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Autocrine amplification of PAF‐acether formation in immunologically activated murine macrophages
Author(s) -
Ninio Ewa,
Maiza Hassina,
Bidault Jocelyne
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.54.4.296
Subject(s) - platelet activating factor , acetyltransferase , biology , biochemistry , autocrine signalling , receptor , endogeny , macrophage , microbiology and biotechnology , in vitro , acetylation , immunology , gene
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 Cl 6:0 alkyl chain (57% ± 7, mean ± SD, n = 3) and PAF Cl8:1. The PAF‐like material obtained from the propionyl‐CoA‐ supplemented macrophages was a mixture of the propi‐ onyl 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 μΜ) and WEB 2086 (3 μΜ), did not influence the rate of PAF synthesis in the presence of either acetyl‐CoA or pro‐ pionyl‐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.