Effect of 15-lipoxygenase-derived arachidonate metabolites on human neutrophil degranulation

Prostaglandins Leukot Med. 1985 Feb;17(2):199-212. doi: 10.1016/0262-1746(85)90107-6.


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.

MeSH terms

  • Exocytosis / drug effects
  • Glucuronidase / metabolism
  • Humans
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Lipoxygenase / metabolism
  • Muramidase / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / ultrastructure
  • Structure-Activity Relationship


  • Hydroxyeicosatetraenoic Acids
  • 5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid
  • Lipoxygenase
  • Muramidase
  • Glucuronidase