Production of arachidonic acid lipoxygenase products during platelet-neutrophil interactions.
We studied interactions of human platelets and neutrophils with particular reference to the arachidonic acid pathway. Suspensions of [3H]-arachidonate-labeled platelets and unlabeled neutrophils were stimulated with ionophore A23187. We detected several radioactive arachidonate metabolites, which are not produced by platelets alone. This included [3H]-labeled leukotriene B4 (LTB4), dihydroxyeicosatetraenoic acid (DHETE) and 5-hydroxyeicosatetraenoic acid (5-HETE). When the platelet product, [3H]12-HETE, was added to ionophore-stimulated neutrophils, DHETE was formed. In addition, when [3H]5-HETE, a neutrophil arachidonate product, was added to stimulated platelets, DHETE was the major metabolite. We, therefore, suggest that upon stimulation, the platelet derived arachidonate can serve as precursor for the neutrophil-derived eicosanoids LTB4 and 5-HETE and that the platelet-derived product 12-HETE can be metabolized to DHETE by stimulated human neutrophils. It would appear that the platelet and neutrophil lipoxygenase pathways take part in cell-cell interactions - an observation which suggests a role for the neutrophils which are present in hemostatic plugs, thrombi and inflammatory processes.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase