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The involvement of endogenous proteases in the secretory process from human mast cells remains to be clarified. A chymotrypsin-like protease inhibitor, N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), blocked both FceRI- and A23187-mediated histamine release from cultured human mast cells at concentrations above 1 microM. At 10 microM, the concentration that completely inhibited FceRI-mediated histamine release, TPCK did not inhibit the chymase activity of the lysate or that in intact cells. The addition of TPCK to cells 30 min before challenge did not affect FceRI- or A23187-mediated Ca2+ mobilization. These findings suggest that a TPCK-sensitive molecule distinct from chymase is involved in a late stage of the process of histamine release from mast cells in man.
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