Open AccessEnhanced Production of Platelet-Activating Factor in Stimulated Rat Leukocytes Caused by the Blockade of Lysophospholipid Acylation
Author(s) -
Hiroaki Naraba,
Yohsuke Imai,
Masahiko Hayashi,
Sachiko Ohishi
Publication year - 1993
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.61.109
Subject(s) - acylation , blockade , platelet activating factor , platelet , chemistry , pharmacology , biology , endocrinology , immunology , biochemistry , receptor , catalysis
We have previously reported that triacsin C, an acyl-CoA synthetase inhibitor, enhanced the production of platelet-activating factor (PAF) in calcium ionophore-activated rat polymorphonuclear leukocytes (PMNs). In this report, we further demonstrated that the production of PAF by PMNs in response to opsonized zymosan was significantly enhanced by pretreatment with triacsin C and also by the pretreatment with merthiolate, which was reported to be an inhibitor of acyl-CoA/lysolecithin acyltransferase. Pretreatment with triacsin C or merthiolate also enhanced the lyso-PAF content in the stimulated PMNs. Addition of lyso-PAF in the incubation mixture of PMNs in the presence of opsonized zymosan augmented the production of PAF. The enhancement of PAF production by lyso-PAF has been reported by several authors, and the importance of lyso-PAF in the remodeling pathway of PAF synthesis has been generally recognized. Therefore, from the above findings, it is assumed that blockades of the reacylation of lyso-phospholipids, by inhibitors such as triacsin C and merthiolate, might lead to accumulation of lyso-PAF and might result in the enhancement of PAF production when the remodeling pathway is active.