Control of mediator release from mast cells.

Abstract

An acute inflammatory response occumng 5 to 10 min following contact with a specific antigen identifies the type I or immediate hypersensitivity reaction. The response is initiated by a calcium-dependent non-cytotoxic secretion from mast cells of granule-associated preformed mediators and newly generated mediators of inflammation. The secondary recruitment of other cells such as eosinophils and neutrophils by mast cell chemotactic factors contribute further to the ensuing inflammatory tissue reaction (Austen, 1979). Mast cells of man (Colman & Godfrey, 1981) and most animal species (Metzger, 1978) have in excess of 1-6 x 108 receptors on their cell surface which specifically bind IgE through high affinity association with the C4 domain of the Fc fragment (KI 108-1010 mol-I) . The availability of rat peritoneal mast cells in dispersed and purified form together with tissue culture techniques to propagate the related rat basophil leukaemia (RBL) cell line has enabled the biochemical characteristics of the IgE-Fc receptor to be studied in detail. The IgE-Fc receptor of RE3L cells has been isolated and characterized as a glycoprotein of 95000 mol. wt (Metzger, 1978) which has immunochemical identity with corresponding receptors of rat mast serosal mast cells (Conrad er al., 1979). The receptor complex of the RBL cell is composed of at least two ionically linked sub-units, alpha and beta, with estimated molecular weights of 45000 and 55000 respectively (Conrad et al., 1979). Only the cell surface alpha sub-unit has the high affinity binding site for IgE, while the beta sub-unit, buried in the phospholipid plasma membrane, may serve to couple the signal to intracellular mechanisms responsible for secretion (Pecoud & Conrad, 1981). The binding of IgE to mast cell Fc receptors is slow, becoming maximum after 1-6 hr of passive