Aggregating and prostanoid-releasing effects of platelet-activating factor and leukotrienes on human polymorphonuclear leukocytes and platelets.
Aggregating and prostanoid-releasing properties of the inflammatory mediators, platelet-activating factor (PAF) and leukotrienes B4, C4 and D4 were studied in human polymorphonuclear leukocytes (PMNL) and in human platelet-rich plasma. Leukotriene B4 (LTB4) and PAF both induced a reversible aggregation of human PMNL with concomitant stimulation of PGE2 formation, whereas LTC4 had no effect on human PMNL. Arachidonic acid (AA) caused an irreversible aggregation of PMNL which was accompanied by formation of both PGE2 and TXB2. Inhibition of TXB2 synthesis by indomethacin or by OKY-1581, a thromboxane synthetase inhibitor, had no effect on the PMNL aggregation induced by LTB4, PAF or AA. Leukotrienes B4, C4 and D4 caused neither aggregation nor TXB2 release in human platelet-rich plasma. PAF, on the other hand, induced a dose-dependent, reversible platelet aggregation which was not accompanied by TXB2 formation nor inhibited by OKY-1581. The present study indicates that in addition to inducing PMNL aggregation, LTB4 is capable of releasing arachidonate metabolites from human PMNL but not from human platelets. Also the responses of PMNL and platelets to PAF seem to differ as the PAF-induced PMNL aggregation was accompanied by increased prostanoid formation whereas the PAF-induced reversible platelet aggregation was obviously independent from arachidonate metabolism.
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D002449:Cell Aggregation / Q000187:drug effects; D015232:Dinoprostone; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D013189:SRS-A / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D010972:Platelet Activating Factor; D011458:Prostaglandins E; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone