694 DIFFERENCES IN TRYPSIN SUBSTRATES AND INHIBITORS ON PMN CHEMOTAXIS AND PHAGOCYTOSIS

Abstract

There are many apparent similarities between PMN chemotaxis and phagocytosis. Previous investigators have suggested that serine esterases are involved in the chemotactic response in so far as a variety of inhibitors and substrate analogues inhibit chemotaxis. We studied the effect of various trypsin inhibitors and a substrate on human PMN chemotaxis and phagocytosis. Reversible inhibition of chemotaxis was demonstrated with the low molecular weight trypsin substrate N-benzoyl-L-arginine ethyl ester (BAEE). The low molecular weight active site titrant, nitrophenyl-P-guanidino benzoate (NPGB) revealed irreversible inhibition of chemotaxis, whereas the low molecular weight inhibitor, benzamidine (BENZ) and the high molecular weight inhibitor, soybean trypsin inhibitor (STI), caused reversible inhibition. The various inhibitors and the substrate gave varying inhibition profiles. The following concentrations gave complete inhibition of chemotaxis: BAEE, 100mM; NPGB, 0.5mM; BENZ, 10mM; STI, 5mM. Neither the active site titrant, NPGB, nor the low molecular weight inhibitor, BENZ, affected phagocytosis as determined by the Maaloe technique at concentrations completely inhibiting chemotaxis. These results may suggest different underlying mechanisms initiating chemotaxis and phagocytosis.