ORCID Profile
0000-0002-2718-4861
Current Organisation
The University of Edinburgh
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Publisher: The American Association of Immunologists
Date: 15-01-2003
DOI: 10.4049/JIMMUNOL.170.2.1027
Abstract: Neutrophil granulocytes have a short lifespan, with their survival limited by a constitutive program of apoptosis. Acceleration of neutrophil apoptosis following ligation of the Fas death receptor is well-documented and TNF-α also has a transient proapoptotic effect. We have studied the role of the death receptor ligand TRAIL in human neutrophils. We identified the presence of mRNAs for TRAIL, TRAIL-R2, and TRAIL-R3, and cell surface expression of TRAIL-R2 and -R3 in neutrophil populations. Neutrophil apoptosis is specifically accelerated by exposure to a leucine zipper-tagged form of TRAIL, which mimics cell surface TRAIL. Using blocking Abs to TRAIL receptors, specifically TRAIL-R2, and a TRAIL-R1:FcR fusion protein, we have excluded a role for TRAIL in regulating constitutive neutrophil apoptosis. No additional proapoptotic effect of leucine zipper TRAIL was identified following TRAIL treatment of neutrophils in the presence of gliotoxin, an inhibitor of NF-κB, suggesting TRAIL does not activate NF-κB in human neutrophils. TRAIL treatment of human neutrophils did not induce a chemotactic response. The susceptibility of neutrophils to TRAIL-mediated apoptosis suggests a role for TRAIL in the regulation of inflammation and may provide a mechanism for clearance of neutrophils from sites of inflammation.
Publisher: Springer Science and Business Media LLC
Date: 2007
DOI: 10.1038/NRI1999
Publisher: Oxford University Press (OUP)
Date: 25-10-2017
DOI: 10.1093/OFID/OFX228
Abstract: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. We performed a case-control (1:2 age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. We included 32 cases and 64 controls with a median age of 52 years 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M IQR, 0.13–0.40) than controls (0.12 IQR, 0.09–0.17 P ≤ .001). When ided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. NCT01056185.
Publisher: Elsevier BV
Date: 06-2011
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SC03298K
Abstract: Force spectroscopy was used to measure the adhesion of Leishmania to synthetic mimics of galectins on the sand fly midgut.
Publisher: The American Association of Immunologists
Date: 15-08-2003
Publisher: American Thoracic Society
Date: 15-02-2007
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Dockrell.