Amplification mechanisms for the enhancement of antigen-mediated mast cell activation

Activation of mast cells in the allergic inflammatory response occurs via the high affinity receptor for IgE (Fc epsilon RI) following receptor aggregation induced by antigen-mediated cross-linking of IgE-occupied Fc epsilon RI. Recent observations suggest this response is profoundly influenced by other factors that reduce the threshold for, and increase the extent of, mast cell activation. For example, under experimental conditions, cell surface receptors such as KIT and specific G protein-coupled receptors synergistically enhance Fc epsilon RI-mediated mast cell degranulation and cytokine production. Activating mutations in critical signaling molecules may also contribute to such responses. In this review, we describe our research exploring the mechanisms regulating these synergistic interactions and, furthermore, discuss the relevance of our observations in the context of clinical considerations.