Stimulation of leukotriene biosynthesis in human blood leukocytes by platelet-derived 12-hydroperoxy-icosatetraenoic acid.

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Abstract
Addition of arachidonic acid to suspensions of human blood leukocytes induces the synthesis of only small amounts of the C-5 lipoxygenase products as demonstrated by high performance liquid chromatography. The coincubation of blood platelets with the leukocytes always resulted in an activation of the C-5 lipoxygenase and formation of (5S)-5-hydroxy-6,8,11,14-eicosatetraenoic acid, (5S,12S)-5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid and leukotriene B4 from exogenous arachidonic acid. The activation of arachidonic acid metabolism in leukocytes was caused by a labile compound because the synthesis of the C-5 lipoxygenase products did not occur when platelets were preincubated for 1 min or more with the substrate prior to the addition of the leukocytes. The use of cyclooxygenase inhibitors did not suppress the activation of the leukocytes by the platelets. The addition of 5,8,11,14-eicosatetraynoic acid, an inhibitor of cyclooxygenase and C-12 and C-15 lipoxygenases, completely suppressed the formation of leukotrienes, although this substance is not an inhibitor of the C-5 lipoxygenase in human leukocytes. This indicated that a product of the C-12 lipoxygenase was likely the mediator of the stimulatory effect of platelets on leukocyte arachidonic acid metabolism. The finding that direct addition of (12S)-12-hydroperoxy-5,8,10,14-eicosatetraenoic acid, but not of the corresponding hydroxy derivative, could activate the leukocyte''s C-5 lipoxygenase confirmed this hypothesis. An interaction between C-12 and C-5 lipoxygenases can apparently promote the formation of leukotrienes. A cooperation between platelets and leukocytes in inflammation and hypersensitivity reactions is possible. The finding provides a new interest for the platelet C-12 lipoxygenase.