Actions of the protease inhibitor phenylmethylsulfonyl fluoride on neutrophil granule enzyme secretion and superoxide production induced by fMet-Leu-Phe and phorbol 12-myristate-13-acetate

The protease inhibitor, phenylmethylsulfonyl fluoride inhibits granule enzyme release and, above 1 mM, superoxide production from rabbit peritoneal neutrophils induced by the chemotactic peptide, fMet-Leu-Phe. At concentrations below 1 mM, it enhances superoxide production. Superoxide generation stimulated by phorbol 12-myristate-13-acetate is increased by phenylmethylsulfonyl fluoride at all concentrations studied. Phenylmethylsulfonyl fluoride has no effect on the rise in intracellular calcium or the depolarization induced by fMet-Leu-Phe but does decrease the extent of repolarization and abolishes hyperpolarization. It depresses actin polymerization and abolishes cytoplasmic alkalinization caused by fMet-Leu-Phe. The increased phosphorylation induced by phorbol 12-myristate-13-acetate in four of the five proteins studied was not affected by phenylmethylsulfonyl fluoride, but the increased phosphorylation of the fifth, a 21-kD protein was enhanced. We conclude that phenylmethylsulfonyl fluoride acts on inhibitory and enhancing processes or steps induced by fMet-Leu-Phe which are subsequent to or independent of calcium mobilization and protein kinase C activity.