Role of serine esterases in mast cell activation

1 A variety of chymotryptic substrates and inhibitors prevented the release of histamine and prostaglandin D2 from rat peritoneal mast cells stimulated with anti‐IgE but not the calcium ionophore A23187 or a variety of polyamines. 2 The activity of the compounds was strikingly increased in cells reversibly permeabilized with ATP, indicating the importance of their effective incorporation into the cytosol. 3 The compounds produced a comparable inhibition of immunological, but not pharmacological, histamine release from human mast cells and basophils. 4 Treatment of rat mast cells with anti‐IgE led to a marked increase in the 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 enzyme and hydrolysis of the substrate. These changes were attenuated by chymotryptic inhibitors. 6 In total, these data provide compelling evidence for the direct involvement of a serine protease in IgE‐mediated histamine release from mast cells. British Journal of Pharmacology (1998) 123, 1267–1273; doi:10.1038/sj.bjp.0701724