A two-fold effect of L-1-tosylamide-2-phenylethyl chloromethyl ketone on the oxidative metabolism of guinea pig phagocytes.

The protease inhibitor, L-1-tosylamide-2-phenylethylchloromethyl ketone (TPCK), stimulated the O2- production, H2O2 generation, oxygen consumption, and the hexose monophosphate shunt of guinea pig peritoneal polymorphs. Other protease inhibitors were not able to stimulate the metabolic burst of these cells. Maximum stimulation was obtained at 100 microM concentration of the compound. No stimulation was seen in human blood polymorphs even at concentrations higher than those effective on guinea pig polymorphs. TPCK also stimulated the oxidative metabolism of guinea pig blood polymorphs and of guinea pig resident peritoneal macrophages. At concentrations which did not stimulate the oxidative metabolism of guinea pig polymorphs, TPCK inhibited the O2- production induced in these cells by treatment with phorbol myristate acetate (PMA) or with other soluble stimuli. Other protease inhibitors also inhibited the respiratory burst induced by PMA. It is concluded that TPCK exerts two effects on the metabolism of guinea pig phagocytes, which are probably mediated by different mechanisms. The inhibitory effect on the PMA-stimulated respiratory burst might be related to the antiprotease activity of TPCK, while the stimulation of the respiratory burst seems to be independent of protease inhibition.