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.
Naraba
H
H
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Imai
Y
Y
Hayashi
M
M
Oh-ishi
S
S
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors; D000215:Acylation; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013849:Thimerosal / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D008246:Lysophospholipids; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D014226:Triazenes; D014665:Vasodilator Agents; D013849:Thimerosal; C034613:triacsin C; D015054:Zymosan; D008243:1-Acylglycerophosphocholine O-Acyltransferase