ORCID Profile
0000-0003-0849-2209
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 26-03-2001
Abstract: Pulmonary surfactant is synthesised in alveolar type II cells and secreted into the lining of the lung in response to ventilation, temperature changes and autonomic neurotransmitters. Type II cells were isolated from the heterothermic marsupial, Sminthopsis crassicaudata. The neurotransmitters, isoproterenol and carbamylcholine chloride significantly increased phosphatidylcholine secretion at 37 degrees C (basal: 14.2%, isoproterenol: 20.1%, carbamylcholine: 17.0%). Temperature reduced the rate of secretion from dunnart type II cells (e.g. basal: 14.2% at 37 degrees C 7.2% at 18 degrees C). However, the change in secretory rate between 37 degrees C and 18 degrees C was less than expected if due to temperature alone (Q10= 1.4). The surfactant secretory pathway is therefore modulated by factors other than and in addition to, temperature. The response of dunnart type II cells to the agonists remained the same at both temperatures. Basal secretion was higher in dunnart type II cells (14.2% in 4 h) than has been reported in rat type II cells (1.9% in 3 h) and consequently, the agonist-stimulated increases in secretion from dunnart type II cells (41% above basal in 4 h) were much lower than observed for rat type II cells (200% above basal in 1.5 h).
Publisher: Informa UK Limited
Date: 03-2010
DOI: 10.1586/EOG.10.4
Publisher: Elsevier BV
Date: 11-2002
DOI: 10.1016/S1095-6433(02)00187-3
Abstract: Pulmonary surfactant is a mixture of lipids and proteins that is secreted by alveolar type II cells in the lungs of all air-breathing vertebrates. Pulmonary surfactant functions to reduce the surface tension in the lungs and, therefore, reduce the work of breathing. In mammals, the embryonic maturation of the surfactant system is controlled by a host of factors, including glucocorticoids, thyroid hormones and autonomic neurotransmitters. We have used a co-culture system of embryonic type II cells and lung fibroblasts to investigate the ability of dexamethasone, tri-iodothyronine (T(3)), adrenaline and carbamylcholine (carbachol) to stimulate the cellular secretion of phosphatidylcholine in the bearded dragon (Pogona vitticeps) at day 55 (approx. 92%) of incubation and following hatching. Adrenaline stimulated surfactant secretion both before and after hatching, whereas carbachol stimulated secretion only at day 55. Glucocorticoids and triiodothyronine together stimulated secretion at day 55 but did not after hatching. Therefore, adrenaline, carbachol, dexamethasone and T(3), are all involved in the development of the surfactant system in the bearded dragon. However, the efficacy of the hormones is attenuated during the developmental process. These differences probably relate to the changes in the cellular environment during development and the specific biology of the bearded dragon.
Publisher: Springer Berlin Heidelberg
Date: 2010
Publisher: Wiley
Date: 27-10-2013
Abstract: With the worldwide obesity epidemic, the proportion of women entering pregnancy overweight or obese has increased significantly in recent years. Babies born to obese women are at an increased risk of respiratory complications at birth and in childhood. In addition to maternal diabetes, there are a number of metabolic changes that the fetus of an overnourished mother experiences in utero that may modulate lung development and represent the mechanisms underlying the increased risk of respiratory complications. Herein we highlight a series of factors associated with the intrauterine environment of an overnourished mother that may impact on fetal lung development and lead to an increased risk of complications at birth or in postnatal life.
Publisher: Informa UK Limited
Date: 1995
DOI: 10.3109/01902149509031751
Abstract: Hyperpnea induced by swimming rats for 30 min decreased the cholesterol/disaturated phospholipid ratio (CHOL/DSP) in the tubular myelin-poor fraction (alv-2), but did not affect the tubular myelin-rich fraction (alv-1). The phenomenon was further illustrated by the marked inverse relationship between CHOL/DSP and DSP. Because such a result could reflect differential release, processing, or reuptake within the alveolar compartment, this study further explored the mechanism in the rat isolated perfused lung (IPL), using radiolabeled CHOL (3H) and DSP (14C). The study also examined whether the decrease in CHOL/DSP with swimming was associated with the increase in either tidal volume (VT), frequency of breathing (f), or both. It was found that whereas a 2.5-fold increase in VT for 15 min in the IPL increased the CHOL/DSP in alv-1 and decreased it in alv-2, a 3-fold increase in f markedly increased the CHOL/DSP in both alveolar subfractions. In apparent contrast, the increases in both VT and f markedly depressed the ratio of the sp act of CHOL/DSP, reflecting a large decrease in the sp act of CHOL in the alveolar compartment. In view of the acute nature of these IPL experiments, it is suggested that the changes reflect the differential release of CHOL and DSP. Furthermore, the marked decrease in sp act of CHOL must reflect a second source of CHOL supplying the alveolar compartment with sterol of low sp act. It is concluded that there is differential handling of surfactant CHOL and DSP in the alveolar compartment of the rat and that the decrease in CHOL/DSP with swimming is due to an increase in VT.
Publisher: Springer Science and Business Media LLC
Date: 11-2016
Abstract: Administration of glucocorticoids (GCs) to women at risk of preterm delivery reduces the newborn's risk of respiratory distress syndrome (RDS) by 35% to 40% however, not all infants respond to this treatment. Fetal growth restriction (FGR) increases the risk of prematurity, perinatal morbidity, and mortality. This review aims to synthesize current evidence reporting the difference in RDS risk between FGR and normally grown infants (Question 1) and whether antenatal GC administration reduces the risk of RDS morbidity in FGR infants (Question 2). Systematic searches were performed, and after screening, a total of 27 and 9 citations were eligible for inclusion for Questions 1 and 2, respectively. In order to answer the two questions, odds ratios and 95% confidence intervals were calculated for all studies. The evidence was equivocal for a difference in risk of RDS in FGR compared with normally grown infants. Despite antenatal GC administration, there was evidence suggesting that the risk of RDS persists in FGR infants. The range of risk of RDS morbidity observed between studies is likely influenced by the definitions (RDS and FGR), gestational age, and small s le sizes of FGR infants evaluated. In addition, RDS morbidity may be related to the heterogeneous nature of FGR etiologies (including maternal, placental, and/or fetal factors). Further understanding of RDS morbidity and responsiveness to current treatments in FGR infants at a range of gestational ages, larger s le sizes, and stratification according to the specific etiology of FGR, may lead to improved respiratory outcomes at birth in this obstetric subpopulation.
Publisher: Elsevier BV
Date: 2002
DOI: 10.1016/S1388-1981(01)00185-8
Abstract: The primary function of pulmonary surfactant is to reduce the surface tension (ST) created at the air-liquid interface in the lung. Surfactant is a complex mixture of lipids and proteins and its function is influenced by physiological parameters such as metabolic rate, body temperature and breathing. In the microchiropteran bat Chalinolobus gouldii these parameters fluctuate throughout a 24 h period. Here we examine the surface activity of surfactant from warm-active and torpid bats at both 24 degrees C and 37 degrees C to establish whether alterations in surfactant composition correlate with changes in surface activity. Bats were housed in a specially constructed bat room at Adelaide University, at 24 degrees C and on a 8:16 h light:dark cycle. Surfactant was collected from bats s led during torpor (25<T(b) 35 degrees C). Alterations in the lipid composition of surfactant occur with changes in the activity cycle. Most notable is an increase in surfactant cholesterol (Chol) with decreases in body temperature [Codd et al., Physiol. Biochem. Zool. 73 (2000) 605-612]. Surfactant from active bats was more surface active at higher temperatures, indicated by lower ST(min) and less film area compression required to reach ST(min) at 37 degrees C than at 24 degrees C. Conversely, surfactant from torpid bats was more active at lower temperatures, indicated by lower ST(min) and less area compression required to reach ST(min) at 24 degrees C than at 37 degrees C. Alterations in the Chol content of bat surfactant appear to be crucial to allow it to achieve low STs during torpor.
Publisher: Wiley
Date: 03-2019
DOI: 10.1111/JPC.14410_94
Publisher: University of Chicago Press
Date: 05-2003
DOI: 10.1086/375434
Publisher: University of Chicago Press
Date: 07-1995
Publisher: American Thoracic Society
Date: 08-1995
DOI: 10.1165/AJRCMB.13.2.7626285
Abstract: In this study, we characterized surfactant lipids from the lungs of the lungfish, Protopterus annectens, Lepidosiren paradoxa, and Neoceratodus fosteri (Sarcopterygiia: Dipnoi). We quantified the types of phospholipids present, the amounts of total phospholipid, disaturated phospholipid (DSP)--purported to be the primary surface tension-controlling agent--and cholesterol (CHOL), an important fluidizer. The surfactant phospholipid profiles of all three lungfish were very similar to each other and those of many other animals reported previously. Phosphatidylcholine was the dominant phospholipid (60% to 80%) phosphatidylglycerol was virtually absent and there was a significant proportion of the combination of phosphatidylserine and phosphatidylinositol (10%). The Australian lungfish N. forsteri possessed a surfactant 5 times richer in CHOL and 2 and 3 times poorer in DSP than the surfactant of the African lungfish P. annectens and the South American lungfish L. paradoxa, respectively. Hence, the CHOL/DSP mass ratio of N. forsteri was 12 and 20 times greater than that of P. annectens and L. paradoxa, respectively. Therefore, the surfactant composition of the two derived species of lungfish (P. annectens and L. paradoxa) very closely resembles that of hibians, whereas surfactant from the primitive lungfish (N. forsteri) is almost identical to that of the primitive air-breathing actinopterygiian fish. Thus, it is likely that pulmonary surfactant had only a single origin, coinciding with that of the vertebrates. As with most nonmammalian vertebrates, it is possible that lungfish surfactant functions as an antiglue at low lung volumes or when the lungs are completely collapsed. Furthermore, it appears that within a species, an increase in lung development correlates with an increase in the relative amount of surfactant cholesterol and a decrease in the phospholipid saturation level.
Publisher: Wiley
Date: 15-12-2016
DOI: 10.1002/CPHY.C150003
Abstract: Surfactant lipids and proteins form a surface active film at the air‐liquid interface of internal gas exchange organs, including swim bladders and lungs. The system is uniquely positioned to meet both the physical challenges associated with a dynamically changing internal air‐liquid interface, and the environmental challenges associated with the foreign pathogens and particles to which the internal surface is exposed. Lungs range from simple, transparent, bag‐like units to complex, multilobed, compartmentalized structures. Despite this anatomical variability, the surfactant system is remarkably conserved. Here, we discuss the evolutionary origin of the surfactant system, which likely predates lungs. We describe the evolution of surfactant structure and function in invertebrates and vertebrates. We focus on changes in lipid and protein composition and surfactant function from its antiadhesive and innate immune to its alveolar stability and structural integrity functions. We discuss the biochemical, hormonal, autonomic, and mechanical factors that regulate normal surfactant secretion in mature animals. We present an analysis of the ontogeny of surfactant development among the vertebrates and the contribution of different regulatory mechanisms that control this development. We also discuss environmental (oxygen), hormonal and biochemical (glucocorticoids and glucose) and pollutant (maternal smoking, alcohol, and common “recreational” drugs) effects that impact surfactant development. On the adult surfactant system, we focus on environmental variables including temperature, pressure, and hypoxia that have shaped its evolution and we discuss the resultant biochemical, biophysical, and cellular adaptations. Finally, we discuss the effect of major modern gaseous and particulate pollutants on the lung and surfactant system. © 2016 American Physiological Society. Compr Physiol 6:363‐422, 2016.
Publisher: Wiley
Date: 23-12-2015
DOI: 10.1113/JP271113
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/839656
Abstract: Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR) is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.DCI.2022.104582
Abstract: The air-liquid interface of the mammalian lung is lined with pulmonary surfactants, a mixture of specific proteins and lipids that serve a dual purpose-enabling air-breathing and protection against pathogens. In mammals, surfactant proteins A (SP-A) and D (SP -D) are involved in innate defence of the lung. Birds seem to lack the SP-D gene, but possess SP-A2, an additional SP-A-like gene. Here we investigated the evolution of the SP-A and SP-D genes using computational gene prediction, homology, simulation modelling and phylogeny with published avian and other vertebrate genomes. PCR was used to confirm the identity and expression of SP-A analogues in various tissue homogenates of zebra finch and turkey. In silico analysis confirmed the absence of SP-D-like genes in all 47 published avian genomes. Zebra finch and turkey SP-A1 and SP-A2 sequences, confirmed by PCR of lung homogenates, were compared with sequenced and in silico predicted vertebrate homologs to construct a phylogenetic tree. The collagen domain of avian SP-A1, especially that of zebra finch, was dramatically shorter than that of mammalian SP-A. Amphibian and reptilian genomes also contain avian-like SP-A2 protein sequences with a collagen domain. NCBI Gnomon-predicted avian and alligator SP-A2 proteins all lacked the collagen domain completely. Both avian SP-A1 and SP-A2 sequences form separate clades, which are most closely related to their closest relatives, the alligators. The C-terminal carbohydrate recognition domain (CRD) of zebra finch SP-A1 was structurally almost identical to that of rat SP-A. In fact, the CRD of SP-A is highly conserved among all the vertebrates. Birds retained a truncated version of mammalian type SP-A1 as well as a non-collagenous C-type lectin, designated SP-A2, while losing the large collagenous SP-D lectin, reflecting their evolutionary trajectory towards a unidirectional respiratory system. In the context of zoonotic infections, how these evolutionary changes affect avian pulmonary surface protection is not clear.
Publisher: Elsevier BV
Date: 07-2020
Publisher: American Physiological Society
Date: 09-2001
DOI: 10.1152/AJPREGU.2001.281.3.R770
Abstract: Pulmonary surfactant (PS), a mixture of phospholipids and proteins secreted by alveolar type II cells, functions to reduce the surface tension in the lungs of all air-breathing vertebrates. Here we examine the control of PS during lung development in a homeothermic egg-laying vertebrate. In mammals, glucocorticoids and autonomic neurotransmitters contribute to the maturation of the surfactant system. We examined whether dexamethasone, epinephrine, and carbamylcholine hydrochloride (agonist for acetylcholine) increased the amount of PS secreted from cultured type II cells of the developing chicken lung. In particular, we wanted to establish whether dexamethasone would increase PS secretion through a process involving lung fibroblasts. We isolated and cocultured type II cells and lung fibroblasts from chickens after 16, 18, and 20 days of incubation and from hatchlings ( day 21). Epinephrine stimulated phosphatidylcholine (PC) secretion at all stages, whereas dexamethasone stimulated secretion of PC at days 16 and 18. Carbamylcholine hydrochloride had no effect at any stage. This is the first study to establish the existence of similar cellular pathways regulating the development of surfactant in chickens and eutherian mammals, despite the vastly different birthing strategies and lung structure and function.
Publisher: Wiley
Date: 09-1998
Publisher: Oxford University Press (OUP)
Date: 04-1998
DOI: 10.1093/ICB/38.2.305
Publisher: CSIRO Publishing
Date: 2003
DOI: 10.1071/RD02087
Abstract: Pulmonary surfactant is a complex mixture of phospholipids (PLs), neutral lipids and proteins that lines the inner surface of the lung. Here it modulates surface tension, thereby increasing lung compliance and preventing the transudation of fluid. In humans, pulmonary surfactant is comprised of approximately 80% PLs, 12% neutral lipids and 8% protein. In most eutherian (i.e. placental) mammals, cholesterol (Chol) comprises approximately 8–10% by weight or 14–20 mol% of both alveolar and lamellar body surfactant. It is regarded as an integral component of pulmonary surfactant, yet few studies have concentrated on its function or control. The lipid composition is highly conserved within the vertebrates, except that surfactant of teleost fish is dominated by cholesterol, whereas tetrapod pulmonary surfactant contains a high proportion of disaturated phospholipids (DSPs). The primitive Australian dipnoan lungfish Neoceratodus forsterii demonstrates a ‘fish-type’ surfactant profile, whereas the other derived dipnoans demonstrate a surfactant profile similar to that of tetrapods. Homology of the surfactant proteins within the vertebrates points to a single evolutionary origin for the system and indicates that fish surfactant is a ‘protosurfactant’. Among the terrestrial tetrapods, the relative proportions of DSPs and cholesterol vary in response to lung structure, habitat and body temperature (T b), but not in relation to phylogeny. The cholesterol content of surfactant is elevated in species with simple saccular lungs or in aquatic species or in species with low T b. The DSP content is highest in complex lungs, particularly of aquatic species or species with high T b. Cholesterol is controlled separately from the PL component in surfactant. For ex le, in heterothermic mammals (i.e. mammals that vary their body temperature), the relative amount of cholesterol increases in cold animals. The rapid changes in the Chol to PL ratio in response to various physiological stimuli suggest that these two components have different turnover rates and may be packaged and processed differently. In mammals, the pulmonary surfactant system develops towards the end of gestation and is characterized by an increase in the saturation of PLs in lung washings and the appearance of surfactant proteins in amniotic fluid. In general, the pattern of surfactant development is highly conserved among the amniotes. This conservation of process is demonstrated by an increase in the amount and saturation of the surfactant PLs in the final stages ( %) of development. Although the ratios of surfactant components (Chol, PL and DSP) are remarkably similar at the time of hatching/birth, the relative timing of the maturation of the lipid profiles differs dramatically between species. The uniformity of composition between species, despite differences in lung morphology, birthing strategy and relationship to each other, implies that the ratios are critical for the onset of pulmonary ventilation. The differences in the timing, on the other hand, appear to relate primarily to birthing strategy and the onset of air breathing. As the amount of cholesterol relative to the phospholipids is highly elevated in immature lungs, the pattern of cholesterol during development and evolution represents an ex le of ontogeny recapitulating phylogeny. The fact that cholesterol is an important component of respiratory structures that are primitive, when they are not in use or developing in an embryo, demonstrates that this substance has important and exciting roles in surfactant. These roles still remain to be explored.
Publisher: Public Library of Science (PLoS)
Date: 26-09-2017
Publisher: Elsevier
Date: 2014
Publisher: American Physiological Society
Date: 11-2002
DOI: 10.1152/AJPREGU.00009.2002
Abstract: Pulmonary surfactant is a mixture of lipids and proteins that controls the surface tension of the fluid lining the inner lung. Its composition is conserved among the vertebrates. Here we hypothesize that the in ovo administration of glucocorticoids and thyroid hormones during late incubation will accelerate surfactant development in the saltwater crocodile, Crocodylus porosus. We also hypothesize that the increased maturation of the type II cells in response to hormone pretreatment will result in enhanced responsiveness of the cells to surfactant secretagogues. We s led embryos at days 60, 68, and 75 of incubation and after hatching. We administered dexamethasone (Dex), 3,5,3′-triiodothyronine (T 3 ), or a combination of both hormones (Dex + T 3 ), 48 and 24 h before each prehatching time point. Lavage analysis indicated that the maturation of the phospholipids (PL) in the lungs of embryonic crocodiles occurs rapidly. Only T 3 and Dex + T 3 increased total PL in lavage at embryonic day 60, but Dex, T 3 , and Dex + T 3 increased PL at day 75. The saturation of the PLs was increased by T 3 and Dex + T 3 at day 68. Swimming exercise did not increase the amount or alter the saturation of the surfactant PLs. Pretreatment of embryos with Dex, T 3 , or Dex + T 3 changed the secretion profiles of the isolated type II cells. Dex + T 3 increased the response of the cells to agonists at days 60and 68. Therefore, glucocorticoids and thyroid hormones regulate surfactant maturation in the crocodile.
Publisher: American Physiological Society
Date: 08-2003
Abstract: Pulmonary surfactant controls the surface tension at the air-liquid interface within the lung. This system had a single evolutionary origin that predates the evolution of the vertebrates and lungs. The lipid composition of surfactant has been subjected to evolutionary selection pressures, particularly temperature, throughout the evolution of the vertebrates.
Publisher: American Physiological Society
Date: 06-1999
DOI: 10.1152/JAPPL.1999.86.6.1959
Abstract: Torpor in the dunnart, Sminthopsis crassicaudata, alters surfactant lipid composition and surface activity. Here we investigated changes in surfactant composition and surface activity over 1 h after rapid arousal from torpor (15–30°C at 1°C/min). We measured total phospholipid (PL), disaturated PL (DSP), and cholesterol (Chol) content of surfactant lavage and surface activity (measured at both 15 and 37°C in the captive bubble surfactometer). Immediately after arousal, Chol decreased (from 4.1 ± 0.05 to 2.8 ± 0.3 mg/g dry lung) and reached warm-active levels by 60 min after arousal. The Chol/DSP and Chol/PL ratios both decreased to warm-active levels 5 min after arousal because PL, DSP, and the DSP/PL ratio remained elevated over the 60 min after arousal. Minimal surface tension and film compressibility at 17 mN/m at 37°C both decreased 5 min after arousal, correlating with rapid changes in surfactant Chol. Therefore, changes in lipids matched changes in surface activity during the postarousal period.
Publisher: Elsevier BV
Date: 07-2000
Publisher: Elsevier BV
Date: 10-2021
Publisher: CRC Press
Date: 13-05-2005
DOI: 10.1201/B14169-4
Publisher: University of Chicago Press
Date: 09-1995
Publisher: The Company of Biologists
Date: 09-2003
DOI: 10.1242/JEB.00519
Abstract: Homeothermic mammals experience pulmonary surfactant dysfunction with relatively small fluctuations in body temperature. However, ground squirrels survive dramatic changes in body temperature during hibernation, when body temperature drops from 37°C to 0-5°C during prolonged torpor bouts. Using type II cells isolated from both warm-active and torpid squirrels, we determined the effect of assay temperature, autonomic agonists and torpor on surfactant secretion. Basal secretion was significantly higher in type II cells isolated from torpid squirrels compared with warm-active squirrels when assayed at the body temperature of the animal from which they were isolated(4°C and 37°C, respectively). A change in assay temperature significantly decreased surfactant secretion. However, the change in secretory rate between 37°C and 4°C was less than expected if due to temperature alone (Q10 range=0.8-1.2). Therefore, the surfactant secretory pathway in squirrel type II cells demonstrates some temperature insensitivity. When incubated at the body temperature of the animal from which the cells were isolated, the adrenergic agonist, isoproterenol, significantly increased surfactant secretion in both warm-active and torpid squirrel type II cells. However, the cholinergic agonist, carbamylcholine chloride, only increased secretion in torpid squirrel type II cells when incubated at 4°C. Torpor did not affect basal cAMP production from isolated type II cells. However, the production of cAMP appears to be upregulated in response to isoproterenol in torpid squirrel type II cells. Thus, at the cellular level, both the secretory and regulatory pathways involved in surfactant secretion are thermally insensitive. Upregulating basal secretion and increasing the sensitivity of type II cells to cholinergic stimulation may be adaptative characteristics of torpor that enable type II cells to function effectively at 0-5°C.
Publisher: Elsevier BV
Date: 05-2001
Publisher: Wiley
Date: 02-01-2003
Publisher: University of Chicago Press
Date: 09-2004
DOI: 10.1086/422058
Abstract: Several times throughout their radiation fish have evolved either lungs or swim bladders as gas-holding structures. Lungs and swim bladders have different ontogenetic origins and can be used either for buoyancy or as an accessory respiratory organ. Therefore, the presence of air-filled bladders or lungs in different groups of fishes is an ex le of convergent evolution. We propose that air breathing could not occur without the presence of a surfactant system and suggest that this system may have originated in epithelial cells lining the pharynx. Here we present new data on the surfactant system in swim bladders of three teleost fish (the air-breathing pirarucu Arapaima gigas and tarpon Megalops cyprinoides and the non-air-breathing New Zealand snapper Pagrus auratus). We determined the presence of surfactant using biochemical, biophysical, and morphological analyses and determined homology using immunohistochemical analysis of the surfactant proteins (SPs). We relate the presence and structure of the surfactant system to those previously described in the swim bladders of another teleost, the goldfish, and those of the air-breathing organs of the other members of the Osteichthyes, the more primitive air-breathing Actinopterygii and the Sarcopterygii. Snapper and tarpon swim bladders are lined with squamous and cuboidal epithelial cells, respectively, containing membrane-bound lamellar bodies. Phosphatidylcholine dominates the phospholipid (PL) profile of lavage material from all fish analyzed to date. The presence of the characteristic surfactant lipids in pirarucu and tarpon, lamellar bodies in tarpon and snapper, SP-B in tarpon and pirarucu lavage, and SPs (A, B, and D) in swim bladder tissue of the tarpon provide strong evidence that the surfactant system of teleosts is homologous with that of other fish and of tetrapods. This study is the first demonstration of the presence of SP-D in the air-breathing organs of nonmammalian species and SP-B in actinopterygian fishes. The extremely high cholesterol/disaturated PL and cholesterol/PL ratios of surfactant extracted from tarpon and pirarucu bladders and the poor surface activity of tarpon surfactant are characteristics of the surfactant system in other fishes. Despite the paraphyletic phylogeny of the Osteichthyes, their surfactant is uniform in composition and may represent the vertebrate protosurfactant.
Publisher: American Physiological Society
Date: 03-2000
DOI: 10.1152/AJPREGU.2000.278.3.R611
Abstract: Pulmonary surfactant, a mixture consisting of phospholipids (PL) and proteins, is secreted by type II cells in the lungs of all air-breathing vertebrates. Virtually nothing is known about the factors that control the secretion of pulmonary surfactant in nonmammalian vertebrates. With the use of type II cell cultures from Australian lungfish, North American bullfrogs, and fat-tailed dunnarts, we describe the autonomic regulation of surfactant secretion among the vertebrates. ACh, but not epinephrine (Epi), stimulated total PL and disaturated PL (DSP) secretion from type II cells isolated from Australian lungfish. Both Epi and ACh stimulated PL and DSP secretion from type II cells of bullfrogs and fat-tailed dunnarts. Neither Epi nor ACh affected the secretion of cholesterol from type II cell cultures of bullfrogs or dunnarts. Pulmonary surfactant secretion may be predominantly controlled by the autonomic nervous system in nonmammalian vertebrates. The parasympathetic nervous system may predominate at lower body temperatures, stimulating surfactant secretion without elevating metabolic rate. Adrenergic influences on the surfactant system may have developed subsequent to the radiation of the tetrapods. Furthermore, ventilatory influences on the surfactant system may have arisen at the time of the evolution of the mammalian bronchoalveolar lung. Further studies using other carefully chosen species from each of the vertebrate groups are required to confirm this hypothesis.
Publisher: Cambridge University Press (CUP)
Date: 07-01-2021
DOI: 10.1017/S204017442000135X
Abstract: Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ , surfactant proteins ( SFTP-A, -B, -C , and -D ), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1 . Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B . However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.
Publisher: American Physiological Society
Date: 06-2016
DOI: 10.1152/AJPREGU.00469.2015
Abstract: Intrauterine growth restriction induced by placental restriction (PR) in sheep leads to chronic hypoxemia and reduced surfactant maturation. The underlying molecular mechanism involves altered regulation of hypoxia signaling by increased prolyl hydroxylase domain (PHD) expression. Here, we evaluated the effect of intratracheal administration of the PHD inhibitor dimethyloxalylglycine (DMOG) on functional, molecular, and structural determinants of lung maturation in the control and PR sheep fetus. There was no effect of DMOG on fetal blood pressure or fetal breathing movements. DMOG reduced lung expression of genes regulating hypoxia signaling ( HIF-3α, ACE1), antioxidant defense ( CAT), lung liquid reabsorption ( SCNN1-A, ATP1-A1, AQP-1, AQP-5), and surfactant maturation ( SFTP-A, SFTP-B, SFTP-C, PCYT1A, LPCAT, ABCA3, LAMP3) in control fetuses. There were very few effects of DMOG on gene expression in the PR fetal lung (reduced lung expression of angiogenic factor ADM, water channel AQP-5, and increased expression of glucose transporter SLC2A1). DMOG administration in controls reduced total lung lavage phosphatidylcholine to the same degree as in PR fetuses. These changes appear to be regulated at the molecular level as there was no effect of DMOG on the percent tissue, air space, or numerical density of SFTP-B positive cells in the control and PR lung. Hence, DMOG administration mimics the effects of PR in reducing surfactant maturation in the lung of control fetuses. The limited responsiveness of the PR fetal lung suggests a potential biochemical limit or reduced plasticity to respond to changes in regulation of hypoxia signaling following exposure to chronic hypoxemia in utero.
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.CBPB.2005.05.035
Abstract: Pulmonary surfactant has previously been shown to change during development, both in composition and function. Adult pinnipeds, unlike adult terrestrial mammals, have an altered lung physiology to cope with the high pressures associated with deep ing. Here, we investigated how surfactant composition and function develop in California sea lions (Zalophus californianus). Phosphatidylinositol was the major anionic phospholipid in the newborn, whereas phosphatidylglycerol was increased in the adult. This increase in phosphatidylglycerol occurred at the expense of phosphatidylinositol and phosphatidylserine. There was a shift from long chain and polyunsaturated phospholipid molecular species in the newborn to shorter chain and mono- and disaturated molecular species in the adult. Cholesterol and SP-B concentrations were also higher in the adult. Adult surfactant could reach a lower equilibrium surface tension, but newborn surfactant could reach a lower minimum surface tension. The composition and function of surfactant from newborn California sea lions suggest that this age group is similar to terrestrial newborn mammals, whereas the adult has a " ing mammal" surfactant that can aid the lung during deep es. The onset of ing is probably a trigger for surfactant development in these animals.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.PRRV.2016.08.011
Abstract: Exposure to altered intrauterine conditions during pregnancy influences both fetal growth and organ development. Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction (IUGR) that may influence the risk of infants experiencing respiratory complications at birth. There are a variety of signalling pathways that contribute to normal fetal lung development at the molecular level. The specific molecular effects of chronic hypoxaemia associated with IUGR on lung development are likely to be dependent on the specific aetiology (maternal, placental and/or fetal factors) that can alter hormone concentrations, oxygen and nutrient transport to the fetus. This review discusses molecular pathways that may contribute to altered fetal lung maturation following exposure to chronic hypoxaemia. Importantly, these studies highlight that the heterogeneity in respiratory outcomes at birth in this obstetric subpopulation are likely determined by the timing, severity and duration of chronic hypoxaemia encountered by the fetus during pregnancy.
Publisher: Wiley
Date: 03-2021
DOI: 10.1111/JMWH.13217
Publisher: American Thoracic Society
Date: 06-1994
DOI: 10.1164/AJRCCM.149.6.8004321
Abstract: We have tested the hypothesis that the composition of alveolar surfactant varies with pattern of breathing and level of fitness. We examined three major components of surfactant, surfactant protein A (SP-A), disaturated phospholipids (DSP), and cholesterol (CHOL) in bronchoalveolar lavage (BAL) fluid from 12 healthy men before and after exercise. Fitness was assessed as work load/heart rate ([kpm.min-1]/[HR.HRmax-1]) achieved during cycling for 30 min at 90% theoretical maximal heart rate. Using a bronchoscope, four 20-ml vols of 0.15 M NaCl at 37 degrees C were instilled and then recovered from first a right upper and then a right lower lobe segmental bronchus. As we found no differences in the BAL from upper and lower lobes, the fluid was combined. We found a direct relationship between CHOL and DSP (rs = 0.84, p < 0.001), SP-A and CHOL (rs = 0.40, p < 0.025), and between SP-A and DSP (rs = 0.44, p < 0.025). The change in the ratios CHOL/DSP, SP-A/CHOL, and SP-A/DSP immediately after exercise was correlated with fitness (rs = -0.56, p < 0.025 rs = 0.75, p < 0.005 rs = 0.62, p < 0.025, respectively). We conclude that the composition of surfactant can change rapidly with exercise in a manner related to fitness, and we suggest that this is consistent with the existence of at least two pools of tissue surfactant of different composition supplying the alveolar compartment.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.RESP.2010.02.014
Abstract: This article examines the manner in which some new methodologies and novel concepts have contributed to our understanding of how pulmonary surfactant reduces alveolar surface tension. Investigations utilizing small angle X-ray diffraction, inverted interface fluorescence microscopy, time of flight-secondary ion mass spectroscopy, atomic force microscopy, two-photon fluorescence microscopy and electrospray mass spectroscopy are highlighted and a new model of ventilation-induced acute lung injury described. This contribution attempts to emphasize how these new approaches have resulted in a fuller appreciation of events presumably occurring at the alveolar interface.
Publisher: Elsevier BV
Date: 07-2000
Publisher: American Physiological Society
Date: 02-2000
DOI: 10.1152/AJPREGU.2000.278.2.R486
Abstract: In birds and oviparous reptiles, hatching is often a lengthy and exhausting process, which commences with pipping followed by lung clearance and pulmonary ventilation. We examined the composition of pulmonary surfactant in the developing lungs of the chicken, Gallus gallus, and of the bearded dragon, Pogona vitticeps. Lung tissue was collected from chicken embryos at days 14, 16, 18 (prepipped), and 20(postpipped) of incubation and from 1 day and 3 wk posthatch and adult animals. In chickens, surfactant protein A mRNA was detected using Northern blot analysis in lung tissue at all stages s led, appearing relatively earlier in development compared with placental mammals. Chickens were lavaged at days 16, 18, and 20 of incubation and 1 day posthatch, whereas bearded dragons were lavaged at day 55, days 57–60 (postpipped), and days 58–61 (posthatched). In both species, total phospholipid (PL) from the lavage increased throughout incubation. Disaturated PL (DSP) was not measurable before 16 days of incubation in the chick embryo nor before 55 days in bearded dragons. However, the percentage of DSP/PL increased markedly throughout late development in both species. Because cholesterol (Chol) remained unchanged, the Chol/PL and Chol/DSP ratios decreased in both species. Thus the Chol and PL components are differentially regulated. The lizard surfactant system develops and matures over a relatively shorter time than that of birds and mammals. This probably reflects the highly precocial nature of hatchling reptiles.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.RESP.2005.03.002
Abstract: Pinnipeds (seals and sea lions) have developed a specialised respiratory system to cope with living in a marine environment. They have a highly reinforced lung that can completely collapse and reinflate during ing without any apparent side effects. These animals may also have a specialised surfactant system to augment the morphological adaptations. The surface activity of surfactant from four species of pinniped (California sea lion, Northern elephant seal, Northern fur seal and Ringed seal) was measured using a captive bubble surfactometer (CBS), and compared to two terrestrial species (sheep and cow). The surfactant of Northern elephant seal, Northern fur seal and Ringed seal was unable to reduce surface tension (gamma) to normal levels after 5 min adsorption (61.2, 36.7, and 46.2 +/- 1.7 mN/m, respectively), but California sea lion was able to reach the levels of the cow and sheep (23.4 mN/m for California sea lion, 21.6 +/- 0.3 and 23.0 +/- 1.5 mN/m for cow and sheep, respectively). All pinnipeds were also unable to obtain the very low gamma(min) achieved by cow (1.4 +/- 0.1 mN/m) and sheep (1.5 +/- 0.4 mN/m). These results suggest that reducing surface tension to very low values is not the primary function of surfactant in pinnipeds as it is in terrestrial mammals, but that an anti-adhesive surfactant is more important to enable the lungs to reopen following collapse during deep ing.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.BBAMEM.2013.03.005
Abstract: Pulmonary surfactant lines the entire alveolar surface, serving primarily to reduce the surface tension at the air-liquid interface. Surfactant films adsorb as a monolayer interspersed with multilayers with surfactant lipids segregating into different phases or domains. Temperature variation, which influences lipid physical properties, affects both the lipid phase segregation and the surface activity of surfactants. In hibernating animals, such as 13-lined ground squirrels, which vary their body temperature, surfactant must be functional over a wide range of temperatures. We hypothesised that surfactant from the 13-lined ground squirrel, Ictidomys tridecemlineatus, would undergo appropriate lipid structural re-arrangements at air-water interfaces to generate phase separation, sufficient to attain the low surface tensions required to remain stable at both low and high body temperatures. Here, we examined pressure-area isotherms at 10, 25 and 37°C and found that surfactant films from both hibernating and summer-active squirrels reached their highest surface pressure on the Wilhelmy-Langmuir balance at 10°C. Epifluorescence microscopy demonstrated that films of hibernating squirrel surfactant display different lipid micro-domain organisation characteristics than surfactant from summer-active squirrels. These differences were also reflected at the nanoscale as determined by atomic force microscopy. Such re-arrangement of lipid domains in the relatively more fluid surfactant films of hibernating squirrels may contribute to overcoming collapse pressures and support low surface tension during the normal breathing cycle at low body temperatures.
Publisher: Wiley
Date: 09-1998
DOI: 10.1111/J.1440-1681.1998.TB02283.X
Abstract: 1. Pulmonary surfactant is a mixture of lipids and proteins that lines the air-liquid interface of the lungs of all vertebrates. In mammals, it functions to reduce and vary surface tension, which helps to decrease the work of breathing, provide alveolar stability and prevent alveolar oedema. The present review examines the evolution and relative importance of these surface activity related functions in the lungs of vertebrates. 2. The surface activity of surfactant from fish, hibians, birds and most reptiles is generally very low, correlating with a low body temperature and a low disaturated phosholipid content of their surfactant. In contrast, the surfactant of those reptiles with a higher preferred body temperature, as well as that of birds and mammals, has a much higher surface activity. 3. The two main functions of surfactant in mammals are to provide alveolar stability and to increase compliance of the relatively stiff bronchoalveolar lung. As the respiratory units of most non-mammalian vertebrates are up to 1000-fold larger and up to 100-fold more compliant, surfactant is not required for these functions. 4. In non-mammals, surfactant appears to act as an anti-glue preventing the adhesion of respiratory surfaces that may occur when the lungs collapse (e.g. during ing, swallowing of prey or on expiration). Surfactant also controls lung fluid balance. These functions can be fulfilled by a surfactant with relatively low surface activity and may represent the primitive functions of surface active material in vertebrate lungs.
Publisher: University of Chicago Press
Date: 09-2000
DOI: 10.1086/317745
Abstract: Pulmonary surfactant is a mixture of phospholipids, neutral lipids, and proteins that controls the surface tension of the fluid lining the lung. Surfactant amounts and composition are influenced by such physiological parameters as metabolic rate, activity, body temperature, and ventilation. Microchiropteran bats experience fluctuations in these parameters throughout their natural daily cycle of activity and torpor. The activity cycle of the microchiropteran bat Chalinolobus gouldii was studied over a 24-h period. Bats were maintained in a room at constant ambient temperature (24 degrees C) on an 8L : 16D cycle. Diurnal changes in the amount and composition of surfactant were measured at 4-h intervals throughout a 24-h period. The C. gouldii were most active at 2 a.m. and were torpid at 2 p.m. Alveolar surfactant increased 1.5-fold immediately after arousal. The proportion of disaturated phospholipid remained constant, while surfactant cholesterol levels increased 1.5-fold during torpor. Alveolar cholesterol in C. gouldii was six times lower than in other mammals. Cholesterol appears to function in maintaining surfactant fluidity during torpor in this species of bat.
Publisher: Elsevier
Date: 2003
Publisher: Informa UK Limited
Date: 1996
DOI: 10.3109/01902149609031775
Abstract: The lungs of all air-breathing vertebrates contain a form of pulmonary surfactant that lines the alveolar air-water interface where it modifies the interfacial surface tension. These pulmonary surfactants all consist of varying amounts of phospholipids (saturated and unsaturated) and cholesterol. The extent of variation between vertebrate groups and between species within a vertebrate group has been attributed to differences in factors such as phylogeny, body temperature, habitat, and lung structure. The influence of these factors on hibian surfactant composition and function has been studied, but the reptiles, which comprise a polyphyletic group of vertebrates, have never been critically examined. The surfactant lipid composition from species belonging to the three groups of reptiles, the Archosauria (crocodiles), Lepidosauria (snakes and lizards), and Anapsida (turtles), has been determined. New data is presented in conjunction with already published data to create an evolutionary framework that concentrates particularly on the influence of phylogeny, body temperature, and lung structure on the composition of the surfactant lipids. Large amounts of pulmonary surfactant were found in all species of reptiles. All species lavaged at 23 degrees C (except C. atrox) demonstrated DSP/PL ratios of 23-33%. Animals with multicameral lungs exhibited an elevated CHOL/DSP ratio compared with species with unicameral lungs. In all groups, phosphatidylcholine (PC) was the dominant (60-80%) phospholipid. Phosphatidylserine and phosphatidylinositol (PS/PI) and sphingomyelin (S) represented the other phospholipids, while phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) were occasionally observed. In two species of lizards (C. nuchalis and P. vitticeps), the saturated fatty acid, palmitic acid (16:0), was the dominant tail group on the phospholipids. Oleic acid (18:1) was the dominant monounsaturated fatty acid, whereas polyunsaturates comprised about a fifth of the total fatty acid profile. Short-term (4 h) changes in temperature did not affect the relative proportions of the fatty acids in either species. Comparison of the current data with previously published literature suggests that phylogeny and habitat do not significantly influence surfactant lipid composition, but body temperature and to a lesser extent lung structure are important determinants of reptilian surfactant lipid composition.
Publisher: American Physiological Society
Date: 04-2010
DOI: 10.1152/AJPLUNG.00226.2009
Abstract: Pulmonary surfactant is synthesized by type II alveolar epithelial cells to regulate the surface tension at the air-liquid interface of the air-breathing lung. Developmental maturation of the surfactant system is controlled by many factors including oxygen, glucose, catecholamines, and cortisol. The intrauterine growth-restricted (IUGR) fetus is hypoxemic and hypoglycemic, with elevated plasma catecholamine and cortisol concentrations. The impact of IUGR on surfactant maturation is unclear. Here we investigate the expression of surfactant protein (SP) A, B, and C in lung tissue of fetal sheep at 133 and 141 days of gestation (term 150 ± 3 days) from control and carunclectomized Merino ewes. Placentally restricted (PR) fetuses had a body weight SD from the mean of control fetuses and a mean gestational Pa O 2 mmHg. PR fetuses had reduced absolute, but not relative, lung weight, decreased plasma glucose concentration, and increased plasma cortisol concentration. Lung SP-A, -B, and -C protein and mRNA expression was reduced in PR compared with control fetuses at both ages. SP-B and -C but not SP-A mRNA expression and SP-A but not SP-B or -C protein expression increased with gestational age. Mean gestational Pa O 2 was positively correlated with SP-A, -B, and -C protein and SP-B and -C mRNA expression in the younger cohort. SP-A and -B gene expression was inversely related to plasma cortisol concentration. Placental restriction, leading to chronic hypoxemia and hypercortisolemia in the carunclectomy model, results in significant inhibition of surfactant maturation. These data suggest that IUGR fetuses are at significant risk of lung complications, especially if born prematurely.
Publisher: Wiley
Date: 2007
DOI: 10.1002/PPUL.20657
Abstract: Lung surfactant comprises mainly phosphatidylcholine (PC) species together with phosphatidylglycerols and surfactant proteins (SP) SP-A to -D. Changes in the concentrations of its principal components dipalmitoyl-PC, palmitoylmyristoyl-PC, palmitoylpalmitoleoyl-PC relative to developmental, structural and physiological differences are only partially understood. Particularly, their attribution to differences in air-liquid interface curvature, compared with dynamic parameters, such as respiratory rate, are controversial. We postulated that during alveolarization the changes in these principal PC components of surfactant differ from those in other phospholipid parameters, and that across endothermic vertebrates their concentrations are related to lung physiology rather than structure. We therefore investigated in rats from postnatal day (d)1 to d42 the pattern of surfactant phospholipids relative to alveolarization (d4-d14), and we discuss these changes in terms of molecular adaptation to pulmonary structure or physiology. Contrary to mammals with advanced alveolarization and increased respiratory rate (RR) at term, concentrations of dipalmitoyl-PC (49-52%) and palmitoylmyristoyl-PC (7-9%) in lung lavage fluid were identical at d1 and d42. At d7-d14, when in rats RR is increased, palmitoyl-myristoyl-PC transiently increased by 2.5- to 3.9-fold at the expense of dipalmitoyl-PC (-32% to 34%) and palmitoyl-palmitoleoyl-PC (-16%). Other lipidomic changes followed essentially different patterns of increase or decrease. Palmitoyl-myristoyl-PC was increased in large aggregates suggesting that it is an integral component of active surfactant. In the overall context of vertebrates, irrespective of age and lung structure, fractions of palmitoyl-myristoyl-PC, dipalmitoyl-PC and palmitoyl-palmitoleoyl-PC correlate with differences in RR rather than alveolar curvature. In adult mammals, however, only concentrations of palmitoyl-palmitoleoyl-PC correlate with RR.
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0925-4439(98)00061-1
Abstract: Pulmonary surfactant is composed of approx. 90% lipids and 10% protein. This review article focusses on the lipid components of surfactant. The first sections will describe the lipid composition of mammalian surfactant and the techniques that have been utilized to study the involvement of these lipids in reducing the surface tension at an air-liquid interface, the main function of pulmonary surfactant. Subsequently, the roles of specific lipids in surfactant will be discussed. For the two main surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol, specific contributions to the overall surface tension reducing properties of surfactant have been indicated. In contrast, the role of the minor phospholipid components and the neutral lipid fraction of surfactant is less clear and requires further study. Recent technical advances, such as fluorescent microscopic techniques, hold great potential for expanding our knowledge of how surfactant lipids, including some of the minor components, function. Interesting information regarding surfactant lipids has also been obtained in studies evaluating the surfactant system in non-mammalian species. In certain non-mammalian species (and at least one marsupial), surfactant lipid composition, most notably disaturated phosphatidylcholine and cholesterol, changes drastically under different conditions such as an alteration in body temperature. The impact of these changes on surfactant function provide insight into the function of these lipids, not only in non-mammalian lungs but also in the surfactant from mammalian species.
Publisher: Elsevier BV
Date: 02-2011
Publisher: Oxford University Press (OUP)
Date: 10-2007
DOI: 10.1093/ICB/ICM079
Abstract: (Orgeig and Daniels) This surfactant symposium reflects the integrative and multidisciplinary aims of the 1st ICRB, by encompassing in vitro and in vivo research, studies of vertebrates and invertebrates, and research across multiple disciplines. We explore the physical and structural challenges that face gas exchange surfaces in vertebrates and insects, by focusing on the role of the surfactant system. Pulmonary surfactant is a complex mixture of lipids and proteins that lines the air-liquid interface of the lungs of all air-breathing vertebrates, where it functions to vary surface tension with changing lung volume. We begin with a discussion of the extraordinary conservation of the blood-gas barrier among vertebrate respiratory organs, which has evolved to be extremely thin, thereby maximizing gas exchange, but simultaneously strong enough to withstand significant distension forces. The principal components of pulmonary surfactant are highly conserved, with a mixed phospholipid and neutral lipid interfacial film that is established, maintained and dynamically regulated by surfactant proteins (SP). A wide variation in the concentrations of in idual components exists, however, and highlights lipidomic as well as proteomic adaptations to different physiological needs. As SP-B deficiency in mammals is lethal, oxidative stress to SP-B is detrimental to the biophysical function of pulmonary surfactant and SP-B is evolutionarily conserved across the vertebrates. It is likely that SP-B was essential for the evolutionary origin of pulmonary surfactant. We discuss three specific issues of the surfactant system to illustrate the ersity of function in animal respiratory structures. (1) Temperature: In vitro analyses of the behavior of different model surfactant films under dynamic conditions of surface tension and temperature suggest that, contrary to previous beliefs, the alveolar film may not have to be substantially enriched in the disaturated phospholipid, dipalmitoylphosphatidylcholine (DPPC), but that similar properties of rate of film formation can be achieved with more fluid films. Using an in vivo model of temperature change, a mammal that enters torpor, we show that film structure and function varies between surfactants isolated from torpid and active animals. (2) Spheres versus tubes: Surfactant is essential for lung stabilization in vertebrates, but its function is not restricted to the spherical alveolus. Instead, surfactant is also important in narrow tubular respiratory structures such as the terminal airways of mammals and the air capillaries of birds. (3). Insect tracheoles: We investigate the structure and function of the insect tracheal system and ask whether pulmonary surfactant also has a role in stabilizing these minute tubules. Our theoretical analysis suggests that a surfactant system may be required, in order to cope with surface tension during processes, such as molting, when the tracheae collapse and fill with water. Hence, despite observations by Wigglesworth in the 1930s of fluid-filled tracheoles, the challenge persists into the 21st century to determine whether this fluid is associated with a pulmonary-type surfactant system. Finally, we summarize the current status of the field and provide ideas for future research.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.BBAMEM.2012.02.021
Abstract: The interfacial surface tension of the lung is regulated by phospholipid-rich pulmonary surfactant films. Small changes in temperature affect surfactant structure and function in vitro. We compared the compositional, thermodynamic and functional properties of surfactant from hibernating and summer-active 13-lined ground squirrels (Ictidomys tridecemlineatus) with porcine surfactant to understand structure-function relationships in surfactant membranes and films. Hibernating squirrels had more surfactant large aggregates with more fluid monounsaturated molecular species than summer-active animals. The latter had more unsaturated species than porcine surfactant. Cold-adapted surfactant membranes displayed gel-to-fluid transitions at lower phase transition temperatures with reduced enthalpy. Both hibernating and summer-active squirrel surfactants exhibited lower enthalpy than porcine surfactant. LAURDAN fluorescence and DPH anisotropy revealed that surfactant bilayers from both groups of squirrels possessed similar ordered phase characteristics at low temperatures. While ground squirrel surfactants functioned well during dynamic cycling at 3, 25, and 37 degrees C, porcine surfactant demonstrated poorer activity at 3 degrees C but was superior at 37 degrees C. Consequently the surfactant composition of ground squirrels confers a greater thermal flexibility relative to homeothermic mammals, while retaining tight lipid packing at low body temperatures. This may represent the most critical feature contributing to sustained stability of the respiratory interface at low lung volumes. Thus, while less effective than porcine surfactant at 37 degrees C, summer-active surfactant functions adequately at both 37 degrees C and 3 degrees C allowing these animals to enter hibernation. Here further compositional alterations occur which improve function at low temperatures by maintaining adequate stability at low lung volumes and when temperature increases during arousal from hibernation.
Publisher: SAGE Publications
Date: 21-08-2015
Abstract: Evaluation of the number of type II alveolar epithelial cells (AECs) is an important measure of the lung’s ability to produce surfactant. Immunohistochemical staining of these cells in lung tissue commonly uses antibodies directed against mature surfactant protein (SP)-C, which is regarded as a reliable SP marker of type II AECs in rodents. There has been no study demonstrating reliable markers for surfactant system maturation by immunohistochemistry in the fetal sheep lung despite being widely used as a model to study lung development. Here we examine staining of a panel of surfactant pro-proteins (pro–SP-B and pro–SP-C) and mature proteins (SP-B and SP-C) in the fetal sheep lung during late gestation in the saccular/alveolar phase of development (120, 130, and 140 days), with term being 150 ± 3 days, to identify the most reliable marker of surfactant producing cells in this species. Results from this study indicate that during late gestation, use of anti-SP-B antibodies in the sheep lung yields significantly higher cell counts in the alveolar epithelium than SP-C antibodies. Furthermore, this study highlights that mature SP-B antibodies are more reliable markers than SP-C antibodies to evaluate surfactant maturation in the fetal sheep lung by immunohistochemistry.
Publisher: American Physiological Society
Date: 1998
DOI: 10.1152/JAPPL.1998.84.1.146
Abstract: Lopatko, Olga V., Sandra Orgeig, Christopher B. Daniels, and David Palmer. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84(1): 146–156, 1998.—Torpor changes the composition of pulmonary surfactant (PS) in the dunnart Sminthopsis crassicaudata [C. Langman, S. Orgeig, and C. B. Daniels. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol. 40): R437–R445, 1996]. Here we investigated the surface activity of PS in vitro. Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the subphase of a Wilhelmy-Langmuir balance at 20°C and stabilized for 20 min. After 4 h of torpor, the adsorption rate increased, and equilibrium surface tension (ST eq ), minimal surface tension (ST min ), and the %area compression required to achieve ST min decreased, compared with the warm-active group. After 8 h of torpor, ST min decreased [from 5.2 ± 0.3 to 4.1 ± 0.3 (SE) mN/m] %area compression required to achieve ST min decreased (from 43.4 ± 1.0 to 27.4 ± 0.8) the rate of adsorption decreased and ST eq increased (from 26.3 ± 0.5 to 38.6 ± 1.3 mN/m). ST-area isotherms of warm-active dunnarts and mice at 20°C had a shoulder on compression and a plateau on expansion. These disappeared on the isotherms of torpid dunnarts. S les of whole lavage (from warm-active and 8-h torpor groups) containing 100 μg phospholipid/ml were studied by using a captive-bubble surfactometer at 37°C. After 8 h of torpor, ST min increased (from 6.4 ± 0.3 to 9.1 ± 0.3 mN/m) and %area compression decreased in the 2nd (from 88.6 ± 1.7 to 82.1 ± 2.0) and 3rd (from 89.1 ± 0.8 to 84.9 ± 1.8) compression-expansion cycles, compared with warm-active dunnarts. ST-area isotherms of warm-active dunnarts at 37°C did not have a shoulder on compression. This shoulder appeared on the isotherms of torpid dunnarts. In conclusion, there is a strong correlation between in vitro changes in surface activity and in vivo changes in lipid composition of PS during torpor, although static lung compliance remained unchanged (see Langman et al. cited above). Surfactant from torpid animals is more active at 20°C and less active at 37°C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts.
Publisher: American Physiological Society
Date: 08-1996
DOI: 10.1152/AJPREGU.1996.271.2.R437
Abstract: Cold profoundly influences lung compliance in homeothermic mammals. Much of this effect has traditionally been attributed to the inactivation of the surfactant system. However, many mammals undergo large fluctuations in body temperature (heterothermic mammals). Here, the surfactant lipid composition and lung compliance of warm-active dunnarts (Sminthopsis crassicaudata) and the homeothermic mouse (Mus musculus) [body temperature (Tb) = 35-37 degrees C] were compared with those of dunnarts killed after 1,4 or 8 h of torpor (Tb 20 degrees C). Lung compliance was measured before and after the removal of surfactant, and tissue compliance was determined by inflating the lung with saline. Relative to total phospholipid (PL), mouse surfactant contained proportionately less phosphatidylinositol but more cholesterol (Chol) and phosphatidylglycerol than that of the dunnart. Lung compliance was lower in dunnarts than in mice, consistent with an allometric effect. Surfactant levels, including total PL, Chol, and disaturated phospholipid (DSP) increased during torpor. The relative proportions of Chol and DSP increased after 4 and 8 h, respectively. In marked contrast to previous studies on the behavior of isolated lungs from homeothermic mammals, in our study the lung compliance of dunnarts remained unchanged throughout torpor. Tissue compliance decreased at 1 and 4 h of torpor, but this decrease was abolished by 8 h. It appears that the surfactant of the dunnarts counteracted the negative effect of tissue compliance at 1 and 4 h, an effect not present in homeothermic mammals. However, because lung compliance was maintained at 1 h of torpor in the absence of a compositional change in surfactant lipids, the changes in lipid composition observed at 4 and 8 h of torpor are thought to relate to functions of surfactant other than that of maintaining lung compliance.
Publisher: Informa UK Limited
Date: 12-10-2022
DOI: 10.1080/02646838.2022.2134848
Abstract: This study examined the intra- and inter-rater reliability of the Recorded Interaction Task (RIT) a novel tool to assess mother-infant bonding via observational methods. Mother-infant bonding describes the reciprocal early emotional connection between mother and infant. Whilst various tools exist to assess mother-infant bonding, many incorrectly confuse this construct with mother-infant attachment. Further, available tools are limited to those that employ self-report methods, thus may reflect perceived behaviour, rather than actual behaviour. The RIT is a novel tool for observational assessment of mother-infant bonding. A standard interaction between mother and infant is recorded, and later assessed against specified bonding-related behaviours. Before its use in research, reliability testing must be undertaken to ensure the RIT may be used consistently. The RIT was administered to 15 mother-infant dyads. Participant recordings were assessed by three trained raters at two time points, using the RIT observation scoring sheet. Intra-rater reliability was determined by comparing scores at each time point for each rater. Inter-rater reliability was determined by assessing reliability of scores at the first time point. Strong intra-rater reliability (ICC >0.86) and fair inter-rater reliability (ICC = 0.55) were observed. The current findings support the RIT's potential to reliably assess mother-infant bonding.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2021
DOI: 10.1038/S41390-021-01489-4
Abstract: In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry. Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1 , hypoxia signaling genes ( HIF-2α , HIF-3α , ADM , and EGLN-3 ), genes regulating sodium movement ( SCNN1-A , SCNN1-B , ATP1-A1 , and ATP1-B1 ), surfactant maturation ( SFTP-B and ABCA3 ), and airway remodeling ( ELN ). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue. Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy. Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development. Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth. In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.
Publisher: MDPI AG
Date: 08-04-2021
Abstract: Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been investigated in MPS IIIA. We measured heparan sulphate (HS), lipids and surfactant proteins (SP) in pulmonary tissue and bronchoalveolar lavage fluid (BALF), and surfactant activity in healthy and diseased mice (20 weeks of age). Heparan sulphate, ganglioside GM3 and bis(monoacylglycero)phosphate (BMP) were increased in MPS IIIA lung tissue. There was an increase in HS and a decrease in BMP and cholesteryl esters (CE) in MPS IIIA BALF. Phospholipid composition remained unchanged, but BALF total phospholipids were reduced (49.70%) in MPS IIIA. There was a reduction in SP-A, -C and -D mRNA, SP-D protein in tissue and SP-A, -C and -D protein in BALF of MPS IIIA mice. Captive bubble surfactometry showed an increase in minimum and maximum surface tension and percent surface area compression, as well as a higher compressibility and hysteresis in MPS IIIA surfactant upon dynamic cycling. Collectively these biochemical and biophysical changes in alveolar surfactant are likely to be detrimental to lung function in MPS IIIA.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.PRRV.2016.10.003
Abstract: More women than not are entering pregnancy either overweight or obese. This presents a significant health care burden with respect to maternal morbidities and offspring complications at birth and in later life. In recent years it has also become clear that maternal obesity is an even greater global health problem than anticipated, because the effects are not limited to the mother but are also programmed in the fetus, known as the 'intergenerational cycle of obestiy'. Despite a large body of epidemiological evidence reporting outcomes of obese pregnancies, including offspring respiratory complications, much less is known about the molecular effects of maternal obesity on fetal lung development. This review focuses on the influence of altered substrate supply associated with the obesogenic intrauterine environment on fetal lung development. Understanding the molecular mechanisms contributing to altered fetal lung development will lead to improved respiratory outcomes for offspring at birth and in later life.
Publisher: Informatics Publishing Limited
Date: 03-11-2017
Abstract: Large aggregate (LA) fraction of the pulmonary surfactant (PS) isolated from five different animals of the vertebrate group, lungfish, chicken, crocodile, stumpie lizard and guinea pig were isolated and characterized. Active pulmonary surfactant components were obtained by chloroform-methanol extraction of the saline suspended LA fraction. Total phospholipid (PL) and protein content were estimated biochemically by standard enzymatic methods. A systematic progression in the PL and protein content was noticed with the developmental sequence of the animals, except the crocodile, which could be due to the difficulty in the PS isolation procedure. em In vitro /em functionality of the solvent spread film was carried out in a Langmuir surface balance by way of surface pressure (π)-area (A) measurements. PS from all the species exhibited reversible compression and expansion cycles. A clear correlation between the maximum attainable surface pressure (π sub max /sub ), also known as the collapse pressure (π sub c /sub ) and the developmental sequence, with some exceptions, could have been established. Langmuir-Blodgett deposits, transferred onto freshly cleaved mica, were imaged by atomic force microscopy for the five different species. DPPC enriched domains showed different dimensions for the five different species. The comprehensive set of studies shed light on the composition, film functionality and structure of the pulmonary surfactants of the vertebrates where a correlation with the evolution sequence is observed.
Publisher: American Physiological Society
Date: 11-2005
DOI: 10.1152/AJPREGU.00496.2004
Abstract: Pulmonary surfactant, a complex mixture of lipids and proteins, lowers the surface tension in terminal air spaces and is crucial for lung function. Within an animal species, surfactant composition can be influenced by development, disease, respiratory rate, and/or body temperature. Here, we analyzed the composition of surfactant in three heterothermic mammals (dunnart, bat, squirrel), displaying different torpor patterns, to determine: 1) whether increases in surfactant cholesterol (Chol) and phospholipid (PL) saturation occur during long-term torpor in squirrels, as in bats and dunnarts 2) whether surfactant proteins change during torpor and 3) whether PL molecular species (molsp) composition is altered. In addition, we analyzed the molsp composition of a further nine mammals (including placental/marsupial and hetero-/homeothermic contrasts) to determine whether phylogeny or thermal behavior determines molsp composition in mammals. We discovered that like bats and dunnarts, surfactant Chol increases during torpor in squirrels. However, changes in PL saturation during torpor may not be universal. Torpor was accompanied by a decrease in surfactant protein A in dunnarts and squirrels, but not in bats, whereas surfactant protein B did not change in any species. Phosphatidylcholine (PC)16:0/16:0 is highly variable between mammals and is not the major PL in the wombat, dunnart, shrew, or Tasmanian devil. An inverse relationship exists between PC16:0/16:0 and two of the major fluidizing components, PC16:0/16:1 and PC16:0/14:0. The PL molsp profile of an animal species is not determined by phylogeny or thermal behavior. We conclude that there is no single PL molsp composition that functions optimally in all mammals rather, surfactant from each animal is unique and tailored to the biology of that animal.
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.RESP.2005.08.001
Abstract: Maintaining a functional pulmonary surfactant system at depth is critical for ing mammals to ensure that inspiration is possible upon re-emergence. The lipid and protein composition of lavage extracts from three pinniped species (California sea lion, Northern elephant seal and Ringed seal) were compared to several terrestrial species. Lavage s les were purified using a NaBr discontinuous gradient. Concentrations of phospholipid classes and molecular species were measured using electrospray ionisation mass spectrometry, cholesterol was measured using high-performance liquid chromatography, surfactant protein A (SP-A) and SP-B were measured using enzyme-linked immunosorbent assays. There were small differences in phospholipid classes, with a lower level of anionic surfactant phospholipids, PG and PI, between ing and terrestrial mammals. There were no differences in PL saturation or SP-A levels between species. PC16:0/14:0, PC16:0/16:1, PC16:0/16:0, long chain PI species and the total concentrations of alkyl-acyl species of PC and PG as a ratio of diacyl species were increased in ing mammals, whereas concentrations of PC16:0/18:1, PG16:0/16:0 and PG16:0/18:1 were decreased. Cholesterol levels were very variable between species and SP-B was very low in ing mammals. These differences may explain the very poor surface activity of pinniped surfactant that we have previously described [Miller, N.J., Daniels, C.B., Schürch, S., Schoel, W.M., Orgeig, S., 2005. The surface activity of pulmonary surfactant from ing mammals. Respir. Physiol. Neurobiol. 150 (2006) 220-232], supporting the hypothesis that pinniped surfactant has primarily an anti-adhesive function to meet the challenges of regularly collapsing lungs.
Publisher: Springer Science and Business Media LLC
Date: 02-1998
DOI: 10.1007/PL00006287
Abstract: Surface tension is reduced at the air-liquid interface in the lung by a mixture of lipids and proteins termed pulmonary surfactant. This study is the first to provide evidence for the presence of a surfactant-specific protein (Surfactant Protein A-SP-A) in the gas-holding structures of representatives of all the major vertebrate groups. Western blot analysis demonstrated cross-reactivity between an antihuman SP-A antibody and material lavaged from lungs or swimbladders of members from all vertebrate groups. Immunocytochemistry localized this SP-A-like protein to the air spaces of lungs from the actinopterygiian fish and lungfish. Northern blot analysis indicated that regions of the mouse SP-A cDNA sequence are complementary to lung mRNA from all species examined. The presence of an SP-A-like protein and SP-A mRNA in members of all the major vertebrate groups implies that the surfactant system had a single evolutionary origin in the vertebrates. Moreover, the evolution of the surfactant system must have been a prerequisite for the evolution of airbreathing. The presence of SP-A in the goldfish swimbladder demonstrates a role for the surfactant system in an organ that is no longer used for airbreathing.
Publisher: American Physiological Society
Date: 09-2014
DOI: 10.1152/AJPREGU.00053.2014
Abstract: Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein ( SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.
Publisher: University of Chicago Press
Date: 11-1999
DOI: 10.1086/316712
Abstract: Surfactant occurs in cyclically inflating and deflating, gas-holding structures of vertebrates to reduce the surface tension of the inner fluid lining, thereby preventing collapse and decreasing the work of inflation. Here we determined the presence of surfactant in material lavaged from the airspace in the gas mantle of the pulmonate snail Helix aspersa. Surfactant is characterized by the presence of disaturated phospholipid (DSP), especially disaturated phosphatidylcholine (PC), lavaged from the airspace, by the presence of lamellated osmiophilic bodies (LBs) in the airspaces and epithelial tissue, and by the ability of the lavage to reduce surface tension of fluid in a surface balance. Lavage had a DSP hospholipid (PL) ratio of 0.085, compared to 0.011 in membranes, with the major PL being PC (45.3%). Cholesterol, the primary fluidizer for pulmonary surfactant, was similar in lavage and in lipids extracted from cell homogenates (cholesterol/PL: 0.04 and 0. 03, respectively). LBs were found in the tissues and airspaces. The surface activity of the lavage material is defined as the ability to reduce surface tension under compression to values much lower than that of water. In addition, surface-active lipids will vary surface tension, increasing it upon inspiration as the surface area expands. By these criteria, the surface activity of lavaged material was poor and most similar to that shown by pulmonary lavage of fish and toads. Snail surfactant displays structures, a biochemical PL profile, and biophysical properties similar to surfactant obtained from primitive fish, teleost swim bladders, the lung of the Dipnoan Neoceratodus forsteri, and the hibian Bufo marinus. However, the cholesterol/PL and cholesterol/DSP ratios are more similar to the hibian B. marinus than to the fish, and this similarity may indicate a crucial physicochemical relationship for these lipids.
Publisher: Springer Science and Business Media LLC
Date: 06-2009
Abstract: Women at risk of preterm labor are commonly treated with antenatal glucocorticoids to reduce neonatal complications, including respiratory distress syndrome. Despite the benefits of antenatal glucocorticoid for neonatal lung function, they are associated with negative cardiovascular outcomes. Among this population, there is a group of intrauterine growth-restricted fetuses in which substrate supply is reduced and these fetuses must undergo a range of cardiovascular adaptations to survive. Interestingly, the cardiovascular changes caused by antenatal glucocorticoid in normally grown fetuses are contrary to the cardiovascular adaptations that the intrauterine growth-restricted fetus must make to survive. Hence, the possibility exists that antenatal glucocorticoid in intrauterine growth-restricted infants may compromise cardiovascular development. This review first provides an overview of general antenatal glucocorticoid effects, before outlining the effects on cardiorespiratory development in normally grown fetuses, the cardiovascular adaptations that occur in the intrauterine growth-restricted fetus and finally integrating this with the very limited evidence for the effect of antenatal glucocorticoid in intrauterine growth-restricted infants.
Publisher: Elsevier
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 12-06-2007
DOI: 10.1007/S00239-006-0083-1
Abstract: Maximum-likelihood models of codon and amino acid substitution were used to analyze the lung-specific surfactant protein C (SP-C) from terrestrial, semi-aquatic, and ing mammals to identify lineages and amino acid sites under positive selection. Site models used the nonsynonymous/synonymous rate ratio (omega) as an indicator of selection pressure. Mechanistic models used physicochemical distances between amino acid substitutions to specify nonsynonymous substitution rates. Site models strongly identified positive selection at different sites in the polar N-terminal extramembrane domain of SP-C in the three ing lineages: site 2 in the cetaceans (whales and dolphins), sites 7, 9, and 10 in the pinnipeds (seals and sea lions), and sites 2, 9, and 10 in the sirenians (dugongs and manatees). The only semi-aquatic contrast to indicate positive selection at site 10 was that including the polar bear, which had the largest body mass of the semi-aquatic species. Analysis of the biophysical properties that were influential in determining the amino acid substitutions showed that isoelectric point, chemical composition of the side chain, polarity, and hydrophobicity were the crucial determinants. Amino acid substitutions at these sites may lead to stronger binding of the N-terminal domain to the surfactant phospholipid film and to increased adsorption of the protein to the air-liquid interface. Both properties are advantageous for the repeated collapse and reinflation of the lung upon ing and resurfacing and may reflect adaptations to the high hydrostatic pressures experienced during ing.
Publisher: European Respiratory Society
Date: 09-2017
Publisher: Elsevier BV
Date: 12-1995
DOI: 10.1016/0034-5687(95)00039-9
Abstract: In mammals, the surface tension of the fluid lining the inner lung greatly contributes to the work of breathing. Surface tension is modified by the secretion of a mixture of surface active lipids and proteins (termed pulmonary surfactant). A disaturated phospholipid (DSP), predominantly dipalmitoylphosphatidylcholine (DPPC), can eliminate surface tension under high dynamic compression. Cholesterol (CHOL) and unsaturated phospholipids (USP) promote respreading upon inflation by converting DPPC to the disordered liquid-crystalline state. It appeared to us that a surfactant rich in DPPC, which has a high phase transition temperature of 41 degrees C, is likely to be of only limited use in the lungs of reptiles, many of which have preferred body temperatures between 20 and 30 degrees C. We review here the presence and composition of surfactant in species from the three subclasses of the Reptilia and relate these to lung structure and function, phylogeny and environmental selection pressures such as body temperature. We also discuss the function of reptilian surfactant and the factors which control surfactant turnover. Large amounts of pulmonary surfactant have been found in all reptiles so far examined. In general, warmer reptiles have greater amounts of surfactant which is also relatively enriched in DSP. Cold lizards (18 degrees C) have significantly elevated levels of surfactant cholesterol. As in all vertebrates, PC is always the dominant phospholipid (60-80%). Unlike mammals, phosphatidylglycerol (PG) is absent, with the exception of one species. The remaining phospholipid groups are present to varying degrees. The saturated fatty acid, palmitic acid (16:0) is the dominant acyl group, oleic acid (18:1) is the dominant mono-unsaturated fatty acid, and polyunsaturates comprise only about 20% of the total fatty acid profile. For two species of dragon lizards, short term changes in temperature do not affect the fatty acids, but protracted periods of cold significantly decrease the presence of 16:0 in turtle lavage (Lau and Keough, Can.J. Biochem. 59: 208-219, 1981). Surfactant appears to function as an antiglue in most reptiles, serving to lower opening pressure, and decrease the work of breathing. However, surface tension forces generally do not influence reptilian lung compliance, suggesting that the primary functions of mammalian surfactant are not necessarily relevant to reptiles.
Publisher: University of Chicago Press
Date: 07-2001
DOI: 10.1086/322158
Abstract: Pulmonary surfactant, consisting predominantly of phosphatidylcholine (PC), is secreted from Type II cells into the lungs of all air-breathing vertebrates, where it functions to reduce surface tension. In mammals, glucocorticoids and thyroid hormones contribute to the maturation of the surfactant system. It is possible that phylogeny, lung structure, and the environment may influence the development of the surfactant system. Here, we investigate the ontogeny of PC secretion from cocultured Type II cells and fibroblasts in the sea turtle, Chelonia mydas, following 58, 62, and 73 d of incubation and after hatching. The influence of glucocorticoids and thyroid hormones on PC secretion was also examined. Basal PC secretion was lowest at day 58 (3%) and reached a maximal secretion rate of 10% posthatch. Dexamethasone (Dex) alone stimulated PC secretion only at day 58. Triiodothyronine (T(3)) stimulated PC secretion in cells isolated from days 58 and 73 embryos and from hatchling turtles. A combination of Dex and T(3) stimulated PC secretion at all time points.
Publisher: Springer Science and Business Media LLC
Date: 10-1994
DOI: 10.1007/BF00302547
Abstract: To analyze the relationship between complement component 3 (C3) and the prevalence of cardiometabolic risk factors and disease activity in the rheumatic diseases having the highest rates of cardiovascular morbidity and mortality: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). This is a cross-sectional study including 200 RA, 80 PsA, 150 axSpA patients and 100 healthy donors. The prevalence of cardiometabolic risk factors [obesity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, apolipoprotein B/apolipoprotein A (apoB/apoA) and atherogenic risks and hypertension] was analyzed. Serum complement C3 levels, inflammatory markers and disease activity were evaluated. Cluster analysis was performed to identify different phenotypes. Receiver operating characteristic (ROC) curve analysis to assess the accuracy of complement C3 as biomarker of insulin resistance and disease activity was carried out. Levels of complement C3, significantly elevated in RA, axSpA and PsA patients, were associated with the prevalence of cardiometabolic risk factors. Hard clustering analysis identified two distinctive phenotypes of patients depending on the complement C3 levels and insulin sensitivity state. Patients from cluster 1, characterized by high levels of complement C3 displayed increased prevalence of cardiometabolic risk factors and high disease activity. ROC curve analysis showed that non-obesity related complement C3 levels allowed to identify insulin resistant patients. Complement C3 is associated with the concomitant increased prevalence of cardiometabolic risk factors in rheumatoid arthritis and spondyloarthritis. Thus, complement C3 should be considered a useful marker of insulin resistance and disease activity in these rheumatic disorders.
Publisher: Elsevier BV
Date: 02-2011
Publisher: Wiley
Date: 07-05-2017
DOI: 10.1113/JP273842
Publisher: Elsevier BV
Date: 05-2001
DOI: 10.1016/S1095-6433(01)00307-5
Abstract: In most eutherian mammals, cholesterol (Chol) comprises approximately 8-10 wt.% or 14-20 mol.% of both alveolar and lamellar body surfactant. It is regarded as an integral component of pulmonary surfactant, yet few studies have concentrated on its function or control. Throughout the evolution of the vertebrates, the contribution of cholesterol relative to surfactant phospholipids decreases, while that of the disaturated phospholipids (DSP) increases. Chol generally appears to dominate in animals with primitive bag-like lungs that lack septation, in the saccular lung of snakes or swimbladders which are not used predominantly for respiration, and also in immature lungs. It is possible that in these systems, cholesterol represents a protosurfactant. Cholesterol is controlled separately from the phospholipid (PL) component in surfactant. For ex le, in heterothermic mammals such as the fat-tailed dunnart, Sminthopsis crassicaudata, and the microchiropteran bat, Chalinolobus gouldii, and also in the lizard, Ctenophorus nuchalis, the relative amount of Chol increases in cold animals. During the late stages of embryonic development in chickens and lizards, the Chol to PL and Chol to DSP ratios decrease dramatically. While in isolated lizard lungs, adrenaline and acetylcholine stimulate the secretion of surfactant PL, Chol secretion remains unaffected. This is also supported in isolated cell studies of lizards and dunnarts. The rapid changes in the Chol to PL ratio in response to various physiological stimuli suggest that these two components have different turnover rates and may be packaged and processed differently. Infusion of [3H]cholesterol into the rat tail vein resulted in a large increase in Chol specific activity within 30 min in the lamellar body (LB) fraction, but over a 48-h period, failed to appear in the alveolar surfactant fraction. Analysis of the limiting membrane of the lamellar bodies revealed a high (76%) concentration of LB cholesterol. The majority of lamellar body Chol is, therefore, not released into the alveolar compartment, as the limiting membrane fuses with the cell membrane upon exocytosis. It appears unlikely, therefore, that lamellar bodies are the major source of alveolar Chol. It is possible that the majority of alveolar Chol is synthesised endogenously within the lung and stored independently from surfactant phospholipids. The role of cholesterol in the limiting membrane of the lamellar body may be to enable fast and easy processing by maintaining the membrane in a relatively fluid state.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2011
DOI: 10.1007/S00360-011-0604-0
Abstract: Lymphangiogenesis, the growth of new lymph vessels, has important roles in both normal and pathological lymphatic function. Despite recent advances, the precise molecular mechanisms behind the lymphangiogenic process remain unclear. The Australian marbled gecko, Christinus marmoratus, voluntarily drops its tail (autotomy) as a predator avoidance strategy. Following autotomy a new tail is regenerated including lymphatic drainage pathways. We examined the molecular control of lymphangiogenesis within the unique model of the regenerating gecko tail. Partial sequences were obtained of the gecko lymphangiogenic growth factors, vascular endothelial growth factor C (VEGF-C) and VEGF-D along with their receptor VEGFR-3. These were highly homologous to other vertebrates. Quantitative real-time polymerase chain reaction (PCR) demonstrated up-regulation of VEGF-C, VEGF-D and VEGFR-3 mRNA expression during the early and middle stages of tail regeneration (between 4 and 9 weeks following autotomy), in late regeneration (12 weeks) and during mid-regeneration (7 and 9 weeks), respectively. VEGF-C and VEGF-D immunostaining was observed lining some lymphatic-like and blood vessels in early-mid tail regeneration, indicating possible associations of the proteins with VEGFRs on endothelia. Keratinocytes and fibroblasts also showed positive staining of VEGF-C and VEGF-D in early-mid tail regeneration. Additionally, VEGF-C was localised in adipose tissue in all tail states examined. This work suggests that specific timings exist for the expression of the lymphangiogenic growth factors, VEGF-C and VEGF-D, and their receptor, VEGF-R3, throughout the regeneration of a functional lymphatic network. Along with localisation data, this suggests potential functions for the growth factors in lymphangiogenesis and angiogenesis throughout tail regeneration.
Publisher: Elsevier BV
Date: 05-2001
DOI: 10.1016/S1095-6433(01)00303-8
Abstract: Richard E. Pattle contributed enormously to the biology of the pulmonary surfactant system. However, Pattle can also be regarded as the founding father of comparative and evolutionary research of the surfactant system. He contributed eight seminal papers of the 167 publications we have located on this topic. In particular, Pattle produced a synthesis interpreting the evolution of the surfactant system that formed the foundation for the area. Prepared 25 years ago this synthesis spawned the three great discoveries in the comparative biology of the surfactant system: (1) that the surfactant system has been highly conserved throughout the enormous radiation of the air breathing vertebrates (2) that temperature is the major selective condition that influences surfactant composition (3) that acting as an anti-adhesive is one primitive and ubiquitous function of vertebrate surfactant. Here we review the literature and history of the comparative and evolutionary biology of the surfactant system and highlight the areas of comparative physiology that will contribute to our understanding of the surfactant system in the future. In our view the surfactant system is a neatly packaged system, located in a single cell and highly conserved, yet spectacularly complex. The surfactant system is one of the best systems we know to examine evolutionary processes in physiology as well as gain important insights into gas transfer by complex organisms.
Publisher: Wiley
Date: 24-08-2017
DOI: 10.1113/JP274528
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Abstract: Our aim was to determine whether fetal exposure to intraamniotic lipopolysaccharide (LPS) persistently alters the lungs following moderate preterm birth. Fetal sheep were exposed to LPS (1 mg/d) or saline from 0.75 to preterm birth at 0.90 of gestation. Eleven weeks after preterm birth, lung structure was unaltered. Interleukin (IL)-1β messenger RNA (mRNA) levels were elevated in lungs of LPS-exposed lambs (P < .05) but IL-1β protein levels were unaltered. Lung mRNA levels of IL-6, IL-8 and tumor necrosis factor α, and percentage of inflammatory cells were not different between groups. Surfactant protein (SP)-A and SP-C mRNA levels and SP-B tissue protein expression were higher in LPS-exposed lambs than controls (all P < .05) however, expression of SP-A and SP-C proteins was reduced. Prenatal LPS exposure causes a persistent increase in gene expression of proinflammatory mediators and surfactant proteins and a decrease in lung tissue SP-A and -C protein expression after preterm birth, which may affect lung immunity.
Publisher: Elsevier BV
Date: 04-1991
DOI: 10.1016/0022-2836(91)90268-B
Abstract: The preparation of hybrid histone octamers with wheat histone H2A variants replacing chicken H2A in the chicken octamer is described. The fidelity of the reconstituted hybrid octamers was confirmed by dimethyl suberimidate cross-linking. Polyglutamic-acid-mediated assembly of these octamers on long DNA and subsequent micrococcal nuclease (MNase) digestion demonstrated that, whereas chicken octamers protected 167 base-pairs (representing 2 full turns of DNA), hybrid histone octamers containing wheat histone H2A(1) with its 19 amino acid residue C-terminal extension protected an additional 16 base pairs of DNA against nuclease digestion. The protection observed by hybrid histone octamers containing wheat histone H2A(3) with both a 15 residue N-terminal and a 19 residue C-terminal extension was identical with that observed with H2A(1)-containing hybrid histone octamers with only the 19 residue C-terminal extension. These results suggest that the role of the C-terminal extension is to bind to DNA of the "linker" region. The thermal denaturation of chicken and hybrid core particles was identical in 10 mM-Tris.HCl.20 mM-NaCl, 0.1 mM-EDTA, confirming that there was no interaction between the basic C-terminal extension and DNA of the core particle. Denaturation in EDTA, however, showed that hybrid core particles had enhanced stability, suggesting that the known conformational change of core particles at very low ionic strength allows the C-terminal extension to bind to core particle DNA under these conditions. A model accounting for the observed MNase protection is presented.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 05-2010
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.BBRC.2003.12.012
Abstract: Marine mammals have a spectacular suite of respiratory adaptations to deal with the extreme pressures associated with deep ing. In particular, maintaining a functional pulmonary surfactant system at depth is critical for marine mammals to ensure that inspiration is possible upon re-emergence. Pulmonary surfactant is secreted from alveolar type II (ATII) cells and is crucial for normal lung function. It is not known whether ATII cells have the ability to continue to secrete pulmonary surfactant under pressure, or how secretion is maintained and controlled. We show here that surfactant secretion in California sea lions (Zalophus californianus) was increased after high pressures (25 and 50 atm) of short duration (30 min), but was unaffected by high pressures of long duration (2 h). This is in contrast to a similar sized terrestrial mammal (sheep), where surfactant secretion was increased after high pressures of both long and short duration. Z. californianus and terrestrial mammals also show similar responses to stimulatory hormones and autonomic neurotransmitters. It therefore seems that an increase in the quantity of surfactant in seal lungs after ing is most likely caused by mechanostimulation induced by pressure and volume changes, and that seals are adapted to maintain constant levels of surfactant under long periods of high pressure.
Publisher: University of Chicago Press
Date: 07-1997
DOI: 10.1086/515847
Abstract: An increase in body temperature in the bearded dragon, Pogona vitticeps, is accompanied by an increase in the amount of pulmonary surfactant, a mixture of proteins and lipids, with the latter consisting predominantly of phospholipid and cholesterol. This increase may result from a temperature-induced change in autonomic input to the lungs, as perfusing the isolated lungs of P. vitticeps with either acetylcholine or adrenaline increases surfactant phospholipid release. However, whether acetylcholine acts via intrapulmonary sympathetic ganglia or directly on alveolar Type II cells is unknown. Moreover, the relative importance of circulating catecholamines and pulmonary sympathetic nerves on the control of the surfactant system is also obscure. Here, we describe the mechanism of the modulation of the surfactant system and the effect of this modulation on lung compliance. The role of acetylcholine was determined by perfusing isolated lungs with acetylcholine, acetylcholine and the ganglionic antagonist hexamethonium, or acetylcholine, hexamethonium, and the muscarinic antagonist atropine. Perfusing with acetylcholine significantly increased phospholipid release but did not affect cholesterol release. While histological examination of the lung revealed the presence of a large autonomic ganglion at the apex, blocking sympathetic ganglia with hexamethonium did not prevent the acetylcholine-mediated increase in phospholipid. However, the increase was inhibited by blocking muscarinic receptors with atropine, which indicates that acetylcholine acts on muscarinic receptors to stimulate phospholipid release. By increasing pulmonary smooth muscle tone, acetylcholine decreased opening pressure and increased static inflation pressures. Plasma levels of noradrenaline and adrenaline increased with increasing temperature and were accompanied by a greater surfactant content in the lungs. While surfactant content was also higher in animals that exercised, plasma levels of adrenaline, noradrenaline, and dopamine were not elevated following exercise. Hence, surfactant release in the lizard lung may increase in response to an increase in plasma catecholamine levels. Acetylcholine, and hence the parasympathetic nervous system, may act to stimulate surfactant release but does not act via pulmonary sympathetic ganglia. We conclude that promoting surfactant secretion via an increase in circulating catecholamines may be inappropriate for a cold lizard with a requirement to conserve energy. As body temperature decreases, release of surfactant via nonadrenergic mechanisms, including cholinergic stimulation, may become increasingly important.
Publisher: Elsevier BV
Date: 07-2000
Publisher: American Physiological Society
Date: 10-1995
DOI: 10.1152/AJPREGU.1995.269.4.R838
Abstract: The amount of pulmonary surfactant in the lungs of the bearded dragon (Pogona vitticeps) increases with increasing body temperature. This increase coincides with a decrease in lung compliance. The relationship between surfactant and lung compliance and the principal stimuli for surfactant release and composition (temperature, ventilatory pattern, and autonomic neurotransmitters) were investigated. We chose to investigate ventilatory pattern (which causes mechanical deformation of the type II cells) and adrenergic agents, because they are the major stimuli for surfactant release in mammals. To examine the effects of body temperature and ventilatory pattern, isolated lungs were ventilated at either 18 or 37 degrees C at different ventilatory regimens. An isolated perfused lung preparation at 27 degrees C was used to analyze the effects of autonomic neurotransmitters. Ventilatory pattern did not affect surfactant release, composition, or lung compliance at either 18 or 37 degrees C. An increase in temperature increased phospholipid reuptake and disproportionately increased cholesterol degradation/uptake. Epinephrine and acetylcholine stimulated phospholipid but not cholesterol release. Removal of surfactant caused a decrease in compliance, regardless of the experimental temperature. Temperature appears to be the principal determinant of lung compliance in the bearded dragon, acting directly to increase the tone of the smooth muscle. Increasing the ambient temperature may result in greater surfactant turnover by increasing cholesterol reuptake/degradation directly and by increasing circulating epinephrine, thereby indirectly increasing phospholipid secretion. We suggest that changing ventilatory pattern may be inadequate as a mechanism for maintaining surfactant homeostasis, given the discontinuous, highly variable reptilian breathing pattern.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Wiley
Date: 22-09-2021
DOI: 10.1113/JP281292
Abstract: Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero . The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery ( ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development. LGUN from 115 to 140 days’ gestation significantly decreased fetal body weight, which was normalized by glucose infusion. LGUN and LGUN+G resulted in decreased fetal plasma glucose concentration, with no change in fetal arterial compared to control. There was no effect of LGUN and LGUN+G on the mRNA expression of surfactant proteins ( SFTP ) and genes regulating surfactant maturation in the fetal lung. However, blood flow in the main pulmonary artery was significantly increased in LGUN, despite no change in blood flow in the left or right pulmonary artery and to the fetal lung. There was a negative relationship between left pulmonary artery flow and to the left lung with SFTP‐B and GLUT1 mRNA expression, while their relationship with VEGFR2 was positive. These results suggest that increased pulmonary blood flow measured by MRI may have an adverse effect on surfactant maturation during fetal lung development. image Maternal undernutrition during gestation alters fetal lung development by impacting surfactant maturation. However, the direction of change remains controversial. We examined the effects of maternal late gestation maternal undernutrition (LGUN) on maternal and fetal outcomes, signalling pathways involved in fetal lung development, pulmonary haemodynamics and oxygen delivery in sheep using a combination of molecular and magnetic resonance imaging (MRI) techniques. LGUN decreased fetal plasma glucose concentration without affecting arterial . Surfactant maturation was not affected however, main pulmonary artery blood flow was significantly increased in the LGUN fetuses. This is the first study to explore the relationship between in utero MRI measures of pulmonary haemodynamics and lung development. Across all treatment groups, left pulmonary artery blood flow and oxygen delivery were negatively correlated with surfactant protein B mRNA and protein expression in late gestation.
Publisher: Wiley
Date: 11-2013
DOI: 10.1002/PHY2.130
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/J.BBRC.2003.08.152
Abstract: Fat-tailed dunnarts, Sminthopsis crassicaudata, survive dramatic changes in body temperature during torpor without experiencing surfactant dysfunction. Adrenergic factors regulate surfactant secretion through beta(2)-adrenergic receptors on alveolar type II cells. Temperature has no effect on the secretory response of dunnart type II cells to adrenergic stimulation. We hypothesise that during torpor, dunnart type II cells up-regulate the number of adrenergic receptors present on type II cells to enable stimulation at lower concentrations of agonist. Here, we isolated type II cells from warm-active (35 degrees C) and torpid (15 degrees C) dunnarts and examined the effects of an in vitro temperature change on the number and activity of adrenergic receptors. Torpor did not affect the beta-adrenergic receptor number. However, we observed a significant decrease in adrenergic receptor number when cells from warm-active animals were incubated at 15 degrees C and when cells from torpid animals were incubated at 37 degrees C. cAMP production was significantly higher in type II cells from torpid dunnarts than warm-active dunnarts and this may contribute, in part, to the temperature insensitivity we have previously observed in the adrenergic regulation of surfactant secretion.
Publisher: American Physiological Society
Date: 11-2002
DOI: 10.1152/AJPREGU.00015.2002
Abstract: We investigated the relationship between glucocorticoids, thyroid hormones, and outer ring and inner ring deiodinases (ORD and IRD) during embryonic development in the saltwater crocodile ( Crocodylus porosus). We treated the embryos with the synthetic glucocorticoid dexamethasone (Dex), 3,3′,5-triiodothyronine (T 3 ), and a combination of these two hormones (Dex + T 3 ). The effects of these treatments were specific in different tissues and at different stages of development and also brought about changes in plasma concentrations of free thyroid hormones and corticosterone. Administration of Dex to crocodile eggs resulted in a decrease in 3,3′,5,5′-tetraiodothyronine (T 4 ) ORD activities in liver and kidney microsomes, and a decrease in the high- K m rT 3 ORD activity in kidney microsomes, on day 60 of incubation. Dex treatment increased the T 4 ORD activity in liver microsomes, but not kidney microsomes, on day 75 of incubation. Dex administration decreased T 3 IRD activity in liver microsomes. However, this decrease did not change plasma-free T 3 concentrations, which suggests that free thyroid hormone levels are likely to be tightly regulated during development.
Publisher: American Physiological Society
Date: 04-1994
DOI: 10.1152/AJPREGU.1994.266.4.R1309
Abstract: Examination of lung washings from primitive air-breathing fishes (ropefish, bichirs, and gar) revealed a lipid-based surfactant with an average disaturated phospholipid-to-total phospholipid ratio five times lower than in mammals. The lung lavage of fishes was exceptionally rich in cholesterol, resulting in average cholesterol-to-phospholipid ratios three times higher, and cholesterol-to-disaturated phospholipid ratios nearly 15 times higher, than those of mammals. Removal of lung surfactant doubled the pressures necessary to initially open the anterior regions of collapsed lungs in all three fish species but had little or no effect on pressures required to fill the lung (i.e., compliance) after the initial opening. The elevated cholesterol content found in pulmonary surfactant of these fishes is consistent with such findings in other ectotherms, suggesting that the proportional elevation of cholesterol may serve to stabilize the fluidity of the lung surfactant over broader temperature ranges. The influence of surfactant on lung opening pressures rather than on compliance contrasts with that seen in mammals and supports an "antiglue" role of pulmonary surfactant in the simpler open-design lungs of lower vertebrates.
Publisher: American Physiological Society
Date: 08-2004
DOI: 10.1152/AJPREGU.00399.2003
Abstract: The surfactant system, a complex mixture of lipids and proteins, controls surface tension in the lung and is crucial for the first breath at birth, and thereafter. Heterokairy is defined as plasticity of a developmental process within an in idual. Here, we provide experimental evidence for the concept of heterokairy, as hypoxia induces a change in the onset and rate of development of surfactant, probably via endogenous glucocorticoids, to produce in iduals capable of surviving early hatching. Chicken eggs were incubated under normoxic (21% O 2 ) conditions throughout or under hypoxic (17% O 2 ) conditions from day 10 of incubation. Embryos were s led at days 16, 18, and 20 and also 24 h after hatching. In a second experiment, dexamethasone (Dex), tri-iodothyronine (T 3 ), or a combination (Dex + T 3 ) was administered 24 and 48 h before each time point. Both hypoxia and Dex accelerated maturation of the surfactant lipids by increasing total phospholipid (PL), disaturated phospholipid (DSP), and cholesterol (Chol) in lavage at days 16 and 18. Maturation of surfactant lipid composition was accelerated, with day 16 %DSP/PL, Chol/DSP, and Chol/PL resembling the ratios of day 20 control animals. The effect of Dex + T 3 was similar to that of Dex alone. Hypoxia increased plasma corticosterone levels at day 16, while plasma T 3 levels were not affected. Hence, exposure to hypoxia during critical developmental windows accelerates surfactant maturation, probably by increasing corticosterone production. This internal modulation of the developmental response to an external stimulus is a demonstration of physiological heterokairy.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: American Physiological Society
Date: 12-1999
DOI: 10.1152/AJPREGU.1999.277.6.R1705
Abstract: Pulmonary surfactant, a mixture consisting of lipids and proteins and secreted by type II cells, functions to reduce the surface tension of the fluid lining of the lung, and thereby decreases the work of breathing. In mammals, surfactant secretion appears to be influenced primarily by the sympathetic nervous system and changes in ventilatory pattern. The parasympathetic nervous system is not believed to affect surfactant secretion in mammals. Very little is known about the factors that control surfactant secretion in nonmammalian vertebrates. Here, a new methodology for the isolation and culture of type II pneumocytes from the lizard Pogona vitticeps is presented. We examined the effects of the major autonomic neurotransmitters, epinephrine (Epi) and ACh, on total phospholipid (PL), disaturated PL (DSP), and cholesterol (Chol) secretion. At 37°C, only Epi stimulated secretion of total PL and DSP from primary cultures of lizard type II cells, and secretion was blocked by the β-adrenoreceptor antagonist propranolol. Neither of the agonists affected Chol secretion. At 18°C, Epi and ACh both stimulated DSP and PL secretion but not Chol secretion. The secretion of surfactant Chol does not appear to be under autonomic control. It appears that the secretion of surfactant PL is predominantly controlled by the autonomic nervous system in lizards. The sympathetic nervous system may control surfactant secretion at high temperatures, whereas the parasympathetic nervous system may predominate at lower body temperatures, stimulating surfactant secretion without elevating metabolic rate.
Publisher: American Thoracic Society
Date: 15-07-2009
Publisher: American Physiological Society
Date: 02-2021
Publisher: Springer Berlin Heidelberg
Date: 2000
Publisher: Wiley
Date: 19-07-2023
DOI: 10.1113/JP284786
Abstract: Chronic fetal hypoxaemia is a common pregnancy complication that increases the risk of infants experiencing respiratory complications at birth. In turn, chronic fetal hypoxaemia promotes oxidative stress, and maternal antioxidant therapy in animal models of hypoxic pregnancy has proven to be protective with regards to fetal growth and cardiovascular development. However, whether antenatal antioxidant therapy confers any benefit on lung development in complicated pregnancies has not yet been investigated. Here, we tested the hypothesis that maternal antenatal treatment with MitoQ will protect the developing lung in hypoxic pregnancy in sheep, a species with similar fetal lung developmental milestones as humans. Maternal treatment with MitoQ during late gestation promoted fetal pulmonary surfactant maturation and an increase in the expression of lung mitochondrial complexes III and V independent of oxygenation. Maternal treatment with MitoQ in hypoxic pregnancy also increased the expression of genes regulating liquid reabsorption in the fetal lung. These data support the hypothesis tested and suggest that MitoQ as an antenatal targeted antioxidant treatment may improve lung maturation in the late gestation fetus. image Chronic fetal hypoxaemia promotes oxidative stress, and maternal antioxidant therapy in hypoxic pregnancy has proven to be protective with regards to fetal growth and cardiovascular development. MitoQ is a targeted antioxidant that uses the cell and the mitochondrial membrane potential to accumulate within the mitochondria. Treatment of healthy or hypoxic pregnancy with MitoQ, increases the expression of key molecules involved in surfactant maturation, lung liquid reabsorption and in mitochondrial proteins driving ATP synthesis in the fetal sheep lung. There were no detrimental effects of MitoQ treatment alone on the molecular components measured in the present study, suggesting that maternal antioxidant treatment has no effect on other components of normal maturation of the surfactant system.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0006-291X(03)01427-X
Abstract: The small microchiropteran bat, Chalinolobus gouldii, undergoes large daily fluctuations in metabolic rate, body temperature, and breathing pattern. These alterations are accompanied by changes in surfactant composition, predominantly an increase in cholesterol relative to phospholipid during torpor. Furthermore, the surface activity changes, such that the surfactant functions most effectively at that temperature which matches the animal's activity state. Here, we examine the surface activity of surfactant from bats during arousal from torpor. Bats were housed at 24 degrees C on an 8:16h light:dark cycle and their surfactant was collected during arousal (28<T(b)<32 degrees C). Surface activity was examined with a Captive Bubble Surfactometer at 24 and 37 degrees C. Surfactant from arousing bats was more active at 37 degrees C than at 24 degrees C, indicated by a lower ST(min) and reduced film area compression required to reach ST(min). It appears that the arousal-induced changes in surfactant composition, i.e., lower levels of cholesterol, inhibit adsorption of surfactant at 24 degrees C. Furthermore, the alterations in surfactant composition during arousal are very rapid, such that the mixture behaves more like surfactant from warm-active bats, and therefore, functions more effectively at 37 degrees C.
Publisher: American Physiological Society
Date: 12-1997
DOI: 10.1152/AJPREGU.1997.273.6.R2013
Abstract: Reptilian lungs are potentially susceptible to fluid disturbances because they have very high pulmonary fluid filtration rates. In mammals, pulmonary surfactant protects the lung from developing alveolar edema. Reptiles also have an order of magnitude more surfactant per square centimeter of respiratory surface area compared with mammals. We investigated the role of reptilian surfactant 1) in the entry of vascularly derived fluid into the alveolar space of the isolated perfused lizard ( Pogona vitticeps) lung and 2) in the removal of accumulated fluid from the alveolar space of the isolated perfused turtle ( Trachemys scripta) lung by both the pulmonary venous and lymphatic circulations. The flux of fluorescent (fluorescein isothiocyanate) inulin from the vasculature into the alveolar compartment increased 60% after the removal of surfactant, but capillary fluid filtration over a 10-min period was not affected. Surfactant removal decreased alveolar inulin clearance by both the pulmonary venous circulation and the pulmonary lymphatic system ∼1.5- and 3-fold, respectively. In reptiles, fluid flux from capillary to air space must occur indirectly via the interstitium. In the absence of surfactant, this may result in interstitial drying, which affects both pulmonary venous and pulmonary lymphatic clearance of alveolar fluid.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.RESP.2011.05.015
Abstract: Pulmonary surfactant fulfils erse functions at the lung air-liquid interface of all air-breathing vertebrates. Neurohormonal regulation of surfactant synthesis and secretion is highly conserved among non-mammalian amniotes. Although the pattern of surfactant lipid maturation is similar among species, the onset and completion differ dramatically. These differences are apparently not determined by phylogeny, but may relate to the timing of development of relative hypoxia as an embryo develops, which is related to birthing strategy. We have proposed that hypoxia is an evolutionary drive for differential surfactant development among species. In mammalian and non-mammalian models, hypoxia induces fetal growth restriction. Depending on the timing of the insult, this may be associated with an acceleration or deceleration of surfactant development. The hypoxic effect may be mediated via hormonal and growth factors, such as glucocorticoids and VEGF. However, the multifactorial nature of mammalian growth restriction models complicates the mechanistic interpretations. Hence, less complex oviparous animal models are required, in which hypoxia can be isolated from maternal influences.
Publisher: Wiley
Date: 2007
DOI: 10.1002/AR.20410
Abstract: Rational treatment of lymphoedema may be improved in the future with a better understanding of the physiological processes involved in the regeneration of new lymphatic vessels (lymphangiogenesis). Many lizard species undergo tail autotomy as a predator escape response and subsequently regenerate nonlymphoedematous tails. Such species may offer novel models for examining lymphangiogenesis. In this lymphoscintigraphic evaluation, three radioactive tracers were employed, (99m)Tc-antimony trisulphide colloid (approximately 10 nm diameter), (99m)Tc-tin fluoride colloid (approximately 2,000 nm (99m)Tc-TFC), and (99m)Tc-diethylenetriaminepentaacetic acid (soluble (99m)Tc-DTPA), to examine lymphatic function in regenerating tails of the Australian marbled gecko, Christinus marmoratus. Rate of local clearance and velocity of migration were determined in geckos with original tails and at 6, 9, 12, and >24 weeks after autotomy. In original-tailed geckos, the smaller radiocolloid was cleared to a greater extent and had a faster lymph velocity than in geckos with regenerated tails. The same parameters measured for larger particles were greater in early regeneration than later. (99m)Tc-TFC did not migrate from the injection site in fully regenerated and original gecko tails, which indicates that larger particles are increasingly impeded as tail regeneration progresses. Soluble (99m)Tc-DTPA diffused from the injection site extremely rapidly via venous capillaries in all tails, confirming that the slower clearance of the colloids is solely via the lymphatics. Differences in clearance and lymph velocity between differently sized colloids throughout tail regeneration may be influenced by changes in surrounding tissue structure density and the lymphatic vessel porosity.
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.CBD.2007.02.003
Abstract: The pulmonary surfactant system of heterothermic mammals must be capable of dealing with the effect of low body temperatures on the physical state of the lipid components. We have shown previously that there is a modest increase in surfactant cholesterol during periods of torpor, however these changes do not fully explain the capacity of surfactant to function under the wide range of physical conditions imposed by torpor. Here we examine indirectly the role of surfactant protein C (SP-C) in adapting to variable body temperatures by testing for the presence of positive (adaptive) selection during evolutionary transitions between heterothermy and homeothermy. We sequenced SP-C from genomic DNA of 32 mammalian species from groups of closely related heterothermic and homeothermic species (contrasts). We used phylogenetic analysis by maximum likelihood estimates of rates of non-synonymous to synonymous substitutions and fully Bayesian inference of these sequences to determine whether the mode of body temperature regulation exerts a selection pressure driving the molecular adaptation of SP-C. The protein sequence of SP-C is highly conserved with synonymous or highly conservative amino acid substitutions being predominant. The evolution of SP-C among mammals is characterised by high codon usage bias and high rates of transition/transversion. The only contrast to show evidence of positive selection was that of the bears (Ursus americanus and U. maritimus). The significance of this result is unclear. We show that SP-C is under strong evolutionary constraints, driven by purifying selection, presumably to maintain protein function despite variation in the mode of body temperature regulation.
Publisher: Elsevier BV
Date: 07-2000
Publisher: Elsevier
Date: 2003
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.RESP.2006.04.012
Abstract: Pulmonary surfactant lines the alveolar air-water interface, varying surface tension with lung volume to increase compliance and prevent adhesion of respiratory surfaces. We examined whether the surfactant system of ing mammals exhibits adaptations for more efficient lung function during ing, to complement other respiratory adaptations. Here we review adaptations at the molecular, compositional, functional and cellular levels and during development for animals beginning life on land and progressing to an aquatic environment. Molecular adaptations to ing were examined in surfactant protein C (SP-C) from terrestrial, semi-aquatic and ing mammals using phylogenetic analyses. Diving species exhibited sites under positive selection in the polar N-terminal domain. These amino acid substitutions may lead to stronger binding of SP-C to the phospholipid film and increased adsorption to the air-liquid interface. The concentration of shorter chain phospholipid molecular species was greater and SP-B levels were lower in ing than terrestrial mammals. This may lead to a greater fluidity and explain the relatively poor surface activity of ing mammal surfactant. There were no consistent differences in cholesterol between ing and terrestrial mammals. Surfactant from newborn California sea lions was similar to that of terrestrial mammals. Secretory activity of alveolar type II epithelial cells of sea lions demonstrated an insensitivity to pressure relative to sheep cells. The poor surface activity of ing mammal surfactant is consistent with the hypothesis that it has an anti-adhesive function that develops after the first entry into the water, with a surfactant film that is better suited to repeated collapse and respreading.
Publisher: Elsevier BV
Date: 07-2000
Publisher: American Physiological Society
Date: 07-2015
DOI: 10.1152/AJPLUNG.00275.2014
Abstract: Experimental placental restriction (PR) by carunclectomy in fetal sheep results in intrauterine growth restriction (IUGR), chronic hypoxemia, increased plasma cortisol, and decreased lung surfactant protein (SP) expression. The mechanisms responsible for decreased SP expression are unknown but may involve decreased glucocorticoid (GC) action or changes in hypoxia signaling. Endometrial caruncles were removed from nonpregnant ewes to induce PR. Lungs were collected from control and PR fetuses at 130–135 ( n = 19) and 139–145 ( n = 28) days of gestation. qRT-PCR and Western blotting were used to quantify lung mRNA and protein expression, respectively, of molecular regulators and downstream targets of the GC and hypoxia-signaling pathways. We confirmed a decrease in SP-A, -B, and -C, but not SP-D, mRNA expression in PR fetuses at both ages. There was a net downregulation of GC signaling with a reduction in GC receptor (GR)-α and -β protein expression and a decrease in the cofactor, GATA-6. GC-responsive genes including transforming growth factor-β1, IL-1β, and β2-adrenergic receptor were not stimulated. Prolyl hydroxylase domain ( PHD) 2 mRNA and protein and PHD3 mRNA expression increased with a concomitant increase in hypoxia-inducible factor-1α ( HIF-1α) and HIF-1β mRNA expression. There was an increase in mRNA expression of several, but not all, hypoxia-responsive genes. Hence, both GC and hypoxia signaling may contribute to reduced SP expression. Although acute hypoxia normally inactivates PHDs, chronic hypoxemia in the PR fetus increased PHD abundance, which normally prevents HIF signaling. This may represent a mechanism by which chronic hypoxemia contributes to the decrease in SP production in the IUGR fetal lung.
Publisher: Elsevier BV
Date: 2010
Publisher: University of Chicago Press
Date: 05-2002
DOI: 10.1086/341999
Abstract: The antioxidant enzyme (AOE) system protects the lung from oxidative damage. The pulmonary surfactant (PS) system lowers the interfacial pressure within the lung, improving lung compliance and aiding lung clearance. In mammals, the AOE and PS systems develop in tandem during the final 10%-20% of gestation. Here, we investigated the development of these systems in the viviparous skink, Tiliqua rugosa. The content of total phospholipid (PL), disaturated phospholipid (DSP), and cholesterol (Chol) increased in lung washings from foetal lizards with advancing gestational age. Similarly, the relative saturation of the PLs increased throughout gestation, with mid-stage 40 foetuses having a DSP/PL equivalent to newborns and adults. Maternal lizards had significantly less total PL, DSP, and Chol than nongravid and newborn lizards however, the relative composition did not differ from nongravid animals. This presumably results from compression of the lungs under the bulk of the developing foetus. The Chol/PL and Chol/DSP ratios declined early in development such that mid-stage 40 embryos had comparable ratios to both newborns and adults. Thus, it appears that the PS system matures in a similar manner in skinks and in mammals. However, the composition of surfactant is complete some weeks before parturition, probably to enable improved survivorship of the precocial young in the event of premature birth. Unlike the surfactant lipids, the AOEs, catalase, superoxide dismutase, and glutathione peroxidase did not differ appreciably throughout gestation. It appears therefore that like the surfactant lipids the AOE system is in readiness for air breathing throughout the latter stages of gestation, possibly in preparation for premature birth. Unlike mammals, the PS and AOE systems develop independently from one another.
Publisher: Elsevier BV
Date: 03-1994
DOI: 10.1016/0034-5687(94)90088-4
Abstract: We examined the composition and function of pulmonary surfactants in hibians inhabiting aquatic and terrestrial habitats with particular regard to the influences of (1) variations in body temperature, (2) external hydrostatic pressure and (3) breathing pattern. Two fully aquatic salamanders, and the completely terrestrial cane toad Bufo marinus (all maintained at 21-23 degrees C) were selected. Whereas one of the salamanders (Siren intermedia) possessed gills and lungs, Amphiuma tridactylum only possessed lungs. We determined the amounts of cholesterol (Chol), disaturated phospholipids (DSP) and total phospholipid (PL) in lavage of all three species, and also determined the types of phospholipids of B. marinus and A. tridactylum. DSP lowers surface tension at the air-water interface in the lung, while Chol and unsaturated phospholipids assist spreading and maintain the DSP in its disordered, liquid-crystalline state at high lung volumes. All three species had significant amounts of pulmonary-type surfactant. The two aquatic salamanders had identical ratios of both Chol/PL and DSP/PL both of which in turn were nearly twice those of B. marinus. All three species had similar Chol/DSP ratios. Aquatic salamanders sustain high external hydrostatic pressures exerted by the aquatic environment and tend to collapse their lungs during expiration. We hypothesize that these salamanders might require a DSP-rich surfactant to prevent the epithelial surfaces from adhering and large amounts of Chol to keep the DSP fluid. The terrestrial B. marinus has less DSP, suggesting a surfactant which is fluid over a large range of temperatures. Possibly, cane toads do not require a DSP rich surfactant as they neither collapse their lungs on deflation, nor experience external hydrostatic pressures promoting lung collapse. The PL profile of B. marinus lavage was similar to that of other frogs and mammals, containing phosphatidylcholine (PC) as the predominant phospholipid together with substantial amounts of phosphatidylglycerol (PG). On the other hand, although A. tridactylum exhibited high levels of PC, it contained phosphatidylinositol (PI) in place of PG, a pattern typical of reptiles and birds.
No related grants have been discovered for Sandra Orgeig.