Effect of 15-lipoxygenase-derived arachidonate metabolites on human neutrophil degranulation.
Products of the 15-lipoxygenase pathway of arachidonate metabolism, prepared by techniques that effectively free them from contaminants, were examined for their ability to influence human neutrophil degranulation. 15(S)-Hydroxyicosatetraenoate [15(S)-HETE], 8(S),15(S)-dihydroxyicosatetraenoate, and 5(S),15(S)-dihydroxyicosatetraenoate did not directly stimulate this response, but 5(S),15(S)-dihydroxyicosatetraenoate (158-5000 nM) enhanced degranulation responses elicited by platelet-activating factor and its structural analogues. It had no such effect on the degranulation responses elicited by a tripeptide chemotactic factor, phorbol myristate acetate, leukotriene B4, or ionophore A23187. In many of these respects, the potentiating actions of 5,15-dihydroxyicosatetraenoate paralleled the actions of 5(S)-hydroxyicosatetraenoate. Indeed, these two metabolites had potentiating actions on platelet-activating factor that were non-additive and, under specific conditions, cross-desensitized each other. Based on the structural specificity demonstrated by these and other mono- and dihydroxyeicosatetraenoates in potentiating platelet-activating factor as well as their mutual cross-desensitizing actions, we suggest that 5-hydroxylated arachidonate metabolites act by a structurally specific receptor to potentiate human neutrophil responses to certain stimuli.
D005089:Exocytosis / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D006893:Hydroxyeicosatetraenoic Acids; C034922:5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid; D008084:Lipoxygenase; D009113:Muramidase; D005966:Glucuronidase