Studies on the mechanism of leukotriene B4 biosynthesis by platelet-polymorphonuclear neutrophil interactions.
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We studied the synthesis of 5-lipoxygenase metabolites, especially the mechanism for enhanced leukotriene B4 (LTB4) synthesis by the interaction between human platelets and polymorphonuclear neutrophils (PMNN). Washed cell suspensions (3×107 PMNN and 0-75×107 platelets per ml) were incubated with arachidonic acid (AA) and formylmethionylleucylphenylalanine (FMLP) in the presence of cytochalasin B, and the synthesis of 5-lipoxygense products was analysed by the reversed-phase high-performance liquid chromatography.While incubation of PMNN alone with these stimulants led to the formation of small amounts of the AA metabolites including LTB4, LTB4 production was remarkably activated in the presence of platelets, bearing comparison with that obtained by the incubation of PMNN with calcium ionophore A 23187 and AA. The maximal activation of LTB4 biosynthesis required a definite platelet/PMNN ratio (5-15), FMLP (10μM), cytochalasin B (more than 1μg/ml) and AA (more than 60μM). The maximal LTB4 synthesis was obtained at 3 to 5-min-incubations and decreased thereafter, while the concentration of 5S, 12S-dihydroxyeicosatetraenoic acid (5S, 12S-diHETE) reached a steady level at 1 to 3-min-incubations and did not decrease thereafter. Platelet-release products, such as adenine nucleotides, could not substitute platelets themselves for the stimulatory effect. Prolongation of the interval between the addition of AA and that of FMLP to the cell suspension reduced the LTB4 production. The addition of aspirin to the incubation mixture did not alter the activating effect of platelets. In contrast, lipoxygenase-deficient platelets from a patient with essential thrombocythemia scarecely activated LTB4 biosynthesis.These findings indicate that a labile AA metabolite produced by platelet lipoxygenase, possibly 12-hydroperoxyeicosatetraenoic acid, could potentiate LTB4 biosynthesis in FMLP-stimulated PMNN, and that this platelet-PMNN interaction may play an important role in inflammation and vascular lesions.
- 一般社団法人 日本血栓止血学会の論文
一般社団法人 日本血栓止血学会 | 論文
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