Effect of a Chymotrypsin-like Inhibitor,TPCK, on Histamine Release from Cultured Human Mast Cells

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 FcεRI- and A23187-mediated histamine release from cultured human mast cells at concentrations above 1 μm. At 10 μm, the concentration that completely inhibited FcεI-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 FcεRI- 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.