Effect of 15-lipoxygenase-derived arachidonate metabolites on human neutrophil degranulation. Prostaglandins Leukot Med 1985 Feb;17(2):199-212
Date
02/01/1985Pubmed ID
3920680DOI
10.1016/0262-1746(85)90107-6Scopus ID
2-s2.0-0021924809 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
O'Flaherty JT, Thomas MJAuthor
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ExocytosisGlucuronidase
Humans
Hydroxyeicosatetraenoic Acids
Lipoxygenase
Muramidase
Neutrophils
Structure-Activity Relationship
