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). Although mast cell activation has traditionally been considered an antigen-dependent response mediated via the Fc{epsilon}RI, there is an increasing appreciation that other receptors (and other stimuli) may profoundly influence antigen-mediated degranulation. Furthermore, activating polymorphisms / mutations in, and alternatively spliced forms of receptors and/or signaling proteins may further modulate these responses. Such polymorphisms associated with disease states, for example mastocytosis may be manifested by exacerbated mast cell-dependent physiology. We wish therefore to explore how polymorphisms or alternatively spliced variants of receptors or signaling proteins may produce a hyperactive phenotype. Furhtermore we wish to identify disease states/clinical populations where hyper-responsive and low-responsive mast cells exist and identify signaling defects. Finally, we wish to explore potential approaches for inhibiting these responses.
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| Jensen, B M; Akin, C; Gilfillan, A M (2008) Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders. Br J Pharmacol 154:1572-82 |
| Jensen, Bettina M; Metcalfe, Dean D; Gilfillan, Alasdair M (2007) Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation. Inflamm Allergy Drug Targets 6:57-62 |
