Mast cells play a pivotal role in the pathogenesis of asthma and other allergic diseases. These reactions are generally initiated by antigen-dependent aggregation of the high affinity IgE receptor (Fc-epsilon-RI) expressed on the cell surface and subsequent release of pro-inflammatory mediators (e.g. histamine, prostanoids, proteases and cytokines). We have also demonstrated that interferon-gamma up-regulates the high affinity receptor for IgG (Fc-gamma-RI) on cultured human mast cells and that aggregation of these receptors through IgG leads to mast cell mediator release. Our studies are directed at delineating the signaling pathways initiated by Fc-epsilon-RI and Fc-gamma-RI receptors. The signaling pathways linking the Fc aggregation to human mast cell activation have yet to be delineated. It is now possible to grow human mast cells from a CD34-positive, pluripotent cell population in primary culture with sufficient number and purity to study defined signaling events. Thus, we have been examining specific signaling pathways involved in Fc-epsilon-RI- and Fc-gamma-RI- dependent inflammatory mediator release from human mast cells. The goal is to identify new therapeutic targets in the treatment of allergic diseases.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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