Distinct inhibition of membrane-bound and lysosomal phospholipase A2 by glucocorticoid-induced proteins.

Anti-inflammatory steroids induce the release in vivo of antiphospholipase proteins (APP) into the peritoneal cavities of rats. APP were partially purified by ion- exchange chromatography. The main anti-phospholipase activity was recovered in two zones of the elution gradient named APP I and APP II; their molecular weight (mol. wt) was determined with molecular sieve chromatography. Two phospholipase A2 (PLA2) activities were identified from rat peritoneal leucocytes, one with a pH optimum at 4.5 (a lysosomal enzyme) and one with pH optimum at 8.5 (a membrane-bound enzyme); the selective secretion of the former was observed when leucocytes were stimulated by phagocytosis. The effect of APP on both enzyme activities was studied on enzyme preparations from resting leucocytes. APP were also added to leucocytes incubated with or without phagocytozable material. After incubation, PLA2 activities were determined both inside the cells and in the culture medium. APP I revealed a mol. wt of 200 k with a small fragment of 15 k and inhibited membrane-bound PLA2; APP II revealed a mol. wt of 40 k and inhibited lysosomal PLA2.