Control Of Mast Cell Tryptase Function In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Allergic disorders such as anaphylaxis, eczema, hay fever and asthma affect about 25% of the developed world. Australia has one of the highest asthma prevalence in the world, costing Australians about a billion dollars a year. One of the central players in allergies is the mast cell enzyme, ?-tryptase. We have discovered a new mechanism of control of this enzyme. This research will aid the development of specific and potent inhibitors of ?-tryptase for the treatment of allergic disorders.
Currently in Australia asthma prevalence is high compared with other countries, affecting 10%–12% of adults and 14%–16% of children. This project will determine the contribution of mast cells to the altered function of airway smooth muscle cells and identify how non asthmatic airway smooth muscle inhibits mast cell localisation to it. The findings will provide new targets for asthma therapies and a pathway for prevention strategies, which up until now have been unsuccessful.
Characterization Of Mast Cell Basophil Haematopoesis In Patients With Asthma And Drug Allergies.
Funder
National Health and Medical Research Council
Funding Amount
$412,379.00
Summary
The major emphasis of this investigation is to analyse blood for specific cells thought to be implicated in allergic disease from patients undergoing allergic reactions to medications and in patients with asthma and other allergies. Certain cells in the circulation of these patients are thought to be involved in the clinical manifestation seen in patients with asthma and other allergies. These cells have certain characteristics and for the first time our laboratory has identified a particular ce ....The major emphasis of this investigation is to analyse blood for specific cells thought to be implicated in allergic disease from patients undergoing allergic reactions to medications and in patients with asthma and other allergies. Certain cells in the circulation of these patients are thought to be involved in the clinical manifestation seen in patients with asthma and other allergies. These cells have certain characteristics and for the first time our laboratory has identified a particular cell in the circulation of patients with asthma which we believe may be important in the pathogenesis of this condition. We propose to examine these cells in patients with asthma, those experiencing allergic reactions to drugs and other allergies and determine their characteristics and their growth responses to a number of growth factors which have been demonstrated to affect the growth of cells known as mast cells in the test tube. Once we have characterised these cells in terms of what particular proteins and other products they contain we will then try to correlate the number and type of cell with the clinical allergic state of the patient. Blood will be obtained from patients undergoing acute asthma and those in remission to determine if there is any specific relationship of these cells with acute allergic reactions. We will be also looking at how these cells regulate other physiological systems in the body, in particular possible explanations why patients that suffer acute allergic reactions develop significant drops in blood pressure. We can identify these cells with a specific antibody that we have used in our preliminary studies. This antibody binds the surface of these cells, however the specific protein to which this antibody binds has not been identified. We propose to identify this protein by using molecular biology techniques. These studies will provide us with important insights on the nature of these cells and may lead to new therapies.Read moreRead less
IL-16 Regulates Mast Cell Chemotaxis And Function Through The Tetraspanin CD9.
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Mast cells are found in humans and other mammals at strategic sites such as skin, lining of the airways and gut and provide a first line of defence against a variety of infections. These cells use a number of products that have profound effects in humans. In particular, these products are thought to be involved in defence against bacteria, viruses and are implicated in allergic conditions such as asthma. In normal circumstances mast cells are only found in the tissues and not in the peripheral b ....Mast cells are found in humans and other mammals at strategic sites such as skin, lining of the airways and gut and provide a first line of defence against a variety of infections. These cells use a number of products that have profound effects in humans. In particular, these products are thought to be involved in defence against bacteria, viruses and are implicated in allergic conditions such as asthma. In normal circumstances mast cells are only found in the tissues and not in the peripheral blood. However, we have made the first observation that mast-like cells occur in the peripheral blood of patients with asthma and allergic conditions but not in normals. This finding changed the prevailing paradigm for mast cell biology. The products that can influence mast cell growth and function are vital to the understanding of how mast cells are involved in conditions such as human asthma. We have demonstrated that a protein (CD9) on mast cells in the tetraspanin family is a receptor for a product (IL-16) which is thought to be important in asthma and other inflammatory conditions. The understanding of how mast cells are regulated by IL-16 may lead to potential new therapies in conditions such as asthma and HIV-1 infection.Read moreRead less