Investigate The Role Of PAF And CD40 Ligand In Regulating The Proinflammatory Properties Of Platelets
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlyin ....The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlying the function of both blood cell types is their ability to stick (or adhere) to each other. However the way in which they coordinate this adhesion is very complex. New information from our laboratory has demonstrated that the sticky behaviour of each cell type is spatially and temporally regulated, and may involve may factors both inside and outside of the cells themselves. Our studies aim to define the key components regulating the 'stickiness' of these blood cells, in order to undertand how they contribute to maintaining healthy vessel walls, but also how their stickiness may also contribute to the promotion of diseased vessels. This information will not only increase our knowledge of the factors that regulate blood clot formation, but may also assist in the development of new therapies to prevent and-or treat vessel disease.Read moreRead less
The Role Of Fractalkine In Leukocyte Recruitment In The Periphery
Funder
National Health and Medical Research Council
Funding Amount
$215,196.00
Summary
This research will determine whether a new type of gene plays an important role in inflammation in tissues in the periphery. If it does, we will design strategies to inhibit its function, thereby controlling its effects in inflammation. Such treatment may be useful for diseases such as rheumatoid arthritis, diabetes as well as allergies.
Role Of Adhesion Molecules In Autoimmune Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Lupus is a disease which causes inflammation and pain throughout the body. The inflammation is caused by white blood cells attacking the lining of blood vessels in tissues. The aim of this project is to understand the reasons why these white blood cells attack the blood vessel lining. This process is impossible to study in humans. However, there is a strain of mouse which is affected by a disease which is very similar to human lupus. This disease occurs spontaneously in these mice. Using a micro ....Lupus is a disease which causes inflammation and pain throughout the body. The inflammation is caused by white blood cells attacking the lining of blood vessels in tissues. The aim of this project is to understand the reasons why these white blood cells attack the blood vessel lining. This process is impossible to study in humans. However, there is a strain of mouse which is affected by a disease which is very similar to human lupus. This disease occurs spontaneously in these mice. Using a microscope, it is possible to study the tiny blood vessels which are affected by this disease in these mice . Under the microscope, it is possible to see the white blood cells as they undergo the process of attacking the blood vessel lining. Visualizing this attack then allows us to study it and determine which molecules are important in causing this damaging inflammatory response. Specifically I will examine diseased blood vessels in the skin and brain of these mice, two of the tissues most dramatically affected by this disease. This information should help us gain an increased understanding of lupus as it affects humans.Read moreRead less
Regulation Of Leukocyte Trafficking By Macrophage Migration Inhibitory Factor (MIF).
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The entry of white blood cells in to tissues is a primary event which drives tissue and organ damage in a number of inflammatory and immune mediated conditions. Diseases as diverse as rheumatoid arthritis, lupus or shock due to bacterial infection (septic shock) have many different triggers and manifestations. However almost all autoimmune and inflammatory diseases have one common feature: white blood cells must leave the blood and enter tissue in order to cause tissue inflammation and ultimatel ....The entry of white blood cells in to tissues is a primary event which drives tissue and organ damage in a number of inflammatory and immune mediated conditions. Diseases as diverse as rheumatoid arthritis, lupus or shock due to bacterial infection (septic shock) have many different triggers and manifestations. However almost all autoimmune and inflammatory diseases have one common feature: white blood cells must leave the blood and enter tissue in order to cause tissue inflammation and ultimately tissue damage and loss of function. The mechanism whereby white blood cells leave the blood stream and cross blood vessel walls to get into tissues is a multi-step process often referred to as white blood cell trafficking. Most of the current treatments for immune and inflammatory conditions have the primary aim of keeping white blood cells out of tissue in order to prevent damage. Some of these treatments, like steroids (cortisone), are very effective but cannot be used for prolonged periods because of the risk of problems like bone thinning (osteoporosis), high blood pressure or diabetes. Other treatments and immunosuppressive agents can also be effective but are themselves associated with toxicity and risk of organ damage. Although substantial progress has been made in the management of immune and inflammatory conditions in the last 50 years, the current treatment options are far from ideal. Macrophage migration inhibitory factor (MIF) is an inflammatory substance released by cells which comprise the blood vessel wall as well as by white blood cells themselves. It is known to contribute to the build up of white blood cells in inflamed tissue. The effect of MIF on white blood cell trafficking has never been examined. Understanding how MIF promotes white cell entry in to tissues could be crucial in our understanding of this important process and blocking MIF may prove to be a useful and effective way to prevent it.Read moreRead less
Coordinating Leukocyte Migration And Interaction During Immune Responses: The Multiple And Central Roles Of The Orphan G Protein Coupled Receptor EBI2
Funder
National Health and Medical Research Council
Funding Amount
$512,716.00
Summary
The ability of the immune system to fight infections relies on the capacity of immune cells to navigate within the body. This study aims at understanding the role of the immune cell receptor Epstein-Barr virus-induced gene 2 (EBI2) in guiding the movement and the interaction of the different types of white blood cells during immune responses. These insights will add to our understanding of immune cell migration thereby offering new therapeutic approaches to improve or control immune responses.