Enhanced production of platelet-activating factor in stimulated rat leukocytes caused by the blockade of lysophospholipid acylation.

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.