PRODUCTION OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA BY HUMAN MAST-CELLS - INCREASED ANTI-IGE-DEPENDENT SECRETION AFTER IGE-DEPENDENT ENHANCEMENT OF MAST-CELL IGE-BINDING ABILITY

The contributions of mast cells to the pathology of allergic diseases, as well as to the expression of immunoglobulin E (IgE)-dependent host responses to parasites, reflect both the amounts and types of cytokin es and other mediators that are released by these cells in such settin gs. Whereas mast cells cannot intrinsically express immunologically sp ecific functions, the binding of IgE to high-affinity IgE receptors (F c epsilon RI) on the surface of mast cells primes these cells to secre te cytokines and other biologically active products upon subsequent ex posure to specific antigens. We now report that both HMC-1, a growth f actor-independent human mast cell leukemia cell line, and growth facto r-dependent human umbilical cord blood-derived mast cells can secrete the multifunctional C-C chemokine, macrophage inflammatory protein-1 a lpha (MIP-1 alpha). in addition, we found that in vitro exposure of hu man umbilical cord blood-derived mast cells to concentrations of IgE w ithin the range observed in the serum of subjects with allergic diseas es or parasite infections, which markedly up-regulates the ability of these cells to bind IgE to their surface, also significantly enhances the ability of the cells to secrete MIP-1 alpha: upon subsequent passi ve sensitization with IgE and challenge with anti-IgE. Thus, IgE-depen dent enhancement of human mast cell IgE-binding ability permits these cells to respond to Fc epsilon RI-dependent challenge with significant ly increased secretion of MIP-1 alpha, a chemokine that can have diver se functions in inflammation, allergic reactions, and host responses t o infection.