AUTOCRINE PARACRINE INVOLVEMENT OF PLATELET-ACTIVATING-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA IN THE INDUCTION OF PHOSPHATIDYLSERINE RECOGNITION BY MURINE MACROPHAGES/

The specific recognition of phosphatidylserine (PS) by macrophages is believed to be one means by which effete and apoptotic cells expressin g PS on their outer membrane leaflet are targeted for phagocytosis. Th e aim of this study was to better understand the; autocrine/paracrine factors involved in beta-glucan induction of PS recognition by macroph ages. We provide evidence that both platelet-activating factor (PAF) a nd TGF-beta are involved in beta-glucan induction of PS recognition. T his is based on the observations that the PAF receptor antagonist WEB 2086 and Ab against TGF-beta each could partially inhibit p-glucan-ind uced PS recognition when used alone and could completely inhibit induc tion when used in combination. PAF, like TGF-beta, was found to prime macrophages for PS recognition, which could then be triggered by costi mulation with a nonspecific phagocytic stimulus, latex particles, We a lso provide evidence that the priming by PAF and that by TGF-beta can occur independently of each other. This is based on the observations t hat 1) PAF priming was not blocked by anti-TGF-beta Ab, nor was TGF-be ta priming prevented by WEB 2086; and 2) PAF did not increase the stea dy state level of TGF-beta mRNA, and TGF-P did not induce PAF synthesi s in these cells.