Autocrine amplification of PAF-acether formation in immunologically activated murine macrophages.
When murine macrophages activated in vivo with bacille Calmette-Guérin were triggered with either acetyl-CoA or propionyl-CoA to form PAF-acether (PAF), similar amounts of platelet-aggregating product were recovered. Liquid chromatographic purification and reversed-phase analysis showed that the composition of PAF molecular species formed in the presence of acetyl-CoA was an equimolar mixture of PAF bearing C16:0 alkyl chain (57% +/- 7, mean +/- SD, n = 3) and PAF C18:1. The PAF-like material obtained from the propionyl-CoA-supplemented macrophages was a mixture of the propionyl analogue of PAF (66% +/- 11, n = 3) and native 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 acetyltransferase. Propionyl-PAF triggers the formation of native PAF probably from the endogenous acetyl-CoA pool. Two specific PAF antagonists, BN 52021 (60 microM) and WEB 2086 (3 microM), did not influence the rate of PAF synthesis in the presence of either acetyl-CoA or propionyl-CoA and did 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 amplification of PAF biosynthesis in macrophages.
Ninio
E
E
INSERM U 200, Université Paris Sud, Clamart, France.
Maiza
H
H
Bidault
J
J
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes; D005260:Female; D046934:Ginkgolides; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014230:Triazoles / Q000494:pharmacology
D000214:Acyl Coenzyme A; D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C009061:propionyl-coenzyme A; D000105:Acetyl Coenzyme A; C045856:ginkgolide B