Production of metabolic products of arachidonic acid during cell-cell 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. These included [3H]-labeled leukotriene B4 (LTB4), dihydroxy-eicosatetraeonic acid (DiHETE), and 5-hydroxy-eicosatetraenoic acid (5-HETE). DiHETE was formed when the platelet product [3H]12-HETE was added to ionophore-stimulated neutrophils. In addition, DiHETE was the major metabolite when [3H]5-HETE, a neutrophil arachidonate product, was added to stimulated platelets. We therefore suggest that upon stimulation, platelet-derived arachidonate can serve as precursor for the neutrophil-derived eicosanoids LTB4 and 5-HETE, and the platelet-derived product 12-HETE can be metabolized to DiHETE by stimulated human neutrophils. More recently we have shown that 12-HETE from thrombin-stimulated platelets can also be metabolized to a new product, 12,20-DiHETE, by unstimulated human neutrophils. It would appear that the platelet and neutrophil lipoxygenase pathways take part in cell-cell interactions--an observation that suggests a role for the neutrophils that are present in hemostatic plugs, thrombi, and inflammatory processes.
D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000097:blood*; D001792:Blood Platelets / Q000502:physiology*; D002450:Cell Communication; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000097:blood; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D013189:SRS-A / Q000096:biosynthesis; D013917:Thrombin / Q000502:physiology; D014316:Tritium
D001095:Arachidonic Acids; D013189:SRS-A; D014316:Tritium; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D013917:Thrombin