Anti-Allergic Therapeutics
Research
Allergies and allergic diseases such as asthma are a huge health problem in Australia and the rest-of-the-world. The antibody class immunoglobulin E (IgE) and its high-affinity receptor FcεRI are known to be key components of the allergic process as they are able to trigger activation of potent pro-inflammatory cells called mast cells and basophils. These cells release mediators such as histamine and a variety of cytokines and lipid-derived products. The laboratory aims to develop a clearer understanding of how FcεRI is regulated and how it produces mast cell and basophil activation. We are also interested in the communication that exists between mast cells and other cell types important to asthma pathobiology. In particular how mast cells can regulate the function of airway smooth muscle cells and how this process can be modulated by both IgE and immunoglobulin G (IgG) receptors. Combined, we hope that this knowledge will lead to the development of new and improved anti-allergic and anti-asthma treatments.
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Key References
*Xia YC, Schuliga M, Shepherd M, Powell M, Harris T, Langenbach SY, Tan PS, Gerthoffer WT, Hogarth PM, Stewart AG, Mackay GA. (2011). Functional Expression of IgG-Fc Receptors in Human Airway Smooth Muscle Cells. The American Journal of Respiratory Cell and Molecular Biology, 44, 665-672.
*Xia YC, Sun S, Kuek LE, Lopata AL, Hulett MD, Mackay GA. (2011) Human mast cell line-1 (HMC-1) cells transfected with FcεRIα are sensitive to IgE/antigen-mediated stimulation demonstrating selectivity towards cytokine production. International Immunopharmacology, in press.
*Hernandez-Hansen V, Mackay GA, Lowell CA, Wilson BS and Oliver JM. (2004). The Src kinase Lyn is a negative regulator of mast cell proliferation. The Journal of Leukocyte Biology, 75, 143-151.
*Mackay GA, Hulett MD, Cook JPD, Trist HM, Henry AJ, Sutton BJ, Hogarth PM and Gould HJ. (2002). Mutagenesis within human FcεRIα differentially alters human and murine IgE binding. The Journal of Immunology, 168, 1787-1795.
*Rigby AJ, Epa VC, Mackay GA, Hulett MD, Sutton BJ, Gould HJ and Hogarth PM. (2000). Domain one of the high affinity IgE receptor, FcεRI, regulates binding to IgE through its interface with domain two. The Journal of Biological Chemistry, 275, 9664-9672.
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