ROLE OF SERINE ESTERASES IN MAST-CELL ACTIVATION

1 A variety of chymotryptic substrates and inhibitors prevented the re lease of histamine and prostaglandin D-2 from rat peritoneal mast cell s stimulated with anti-IgE but not the calcium ionophore A23187 or a v ariety of polyamines. 2 The activity of the compounds was strikingly i ncreased in cells reversibly permeabilized with ATP, indicating the im portance of their effective incorporation into the cytosol. 3 The comp ounds produced a comparable inhibition of immunological, but not pharm acological, histamine release from human mast cells and basophils. 4 T reatment of rat mast cells with anti-IgE led to a marked increase in t he total chymotryptic activity expressed by the cells. 5 Immunological , but not pharmacological, stimulation of permeabilized rat mast cells loaded with a fluorescent chymotryptic substrate led to a pronounced and rapid increase in fluorescence, indicating activation of the enzym e and hydrolysis of the substrate. These changes were attenuated by ch ymotryptic inhibitors. 6 In total, these data provide compelling evide nce for the direct involvement of a serine protease in IgE-mediated hi stamine release from mast cells.