AUTOCRINE AMPLIFICATION OF PAF-ACETHER FORMATION IN IMMUNOLOGICALLY ACTIVATED MURINE MACROPHAGES

When murine macrophages activated in vivo with bacille Calmette-Guerin were triggered with either acetyl-CoA or propionyl-CoA to form PAF-ac ether (PAF). similar amounts of platelet-aggregating product were reco vered. Liquid chromatographic purification and reversed-phase analysis showed that the composition of PAF molecular species formed in the pr esence of acetyl-CoA was an equimolar mixture of PAF bearing C16:0 alk yl chain (57% +/- 7, mean +/- SD, n = 3) and PAF C18:1. The PAF-like m aterial obtained from the propionyl-CoA-supplemented macrophages was a mixture of the propionyl analogue of PAF (66% +/- 11, n = 3) and nati ve PAF. The rate of lyso-PAF:acetyl-CoA acetyltransferase (EC 2.3.1.67 ) reaction in a macrophage lysate was similar for either substrate in the presence of an equimolar mixture of propionyl-CoA and acetyl-CoA. We conclude that the exogenously added propionyl-CoA is transferred to lyso-PAF acceptor to form propionyl-PAF by the PAF-forming acetyltran sferase. Propionyl-PAF triggers the formation of native PAF probably f rom the endogenous acetyl-CoA pool. Two specific PAF antagonists, BN 5 2021 (60 muM) and WEB 2086 (3 muM), did not influence the rate of PAF synthesis in the presence of either acetyl-CoA or propionyl-CoA and di d not prevent native PAF formation when propionyl-CoA was added alone, suggesting that the classical PAF receptors are not involved. This is the first description of a possible mechanism of autocrine amplificat ion of PAF biosynthesis in macrophages.