Effects of Exogenous Arachidonic, Eicosapentaenoic, and Docosahexaenoic Acids on the Generation of 5-Lipoxygenase Pathway Products by

Abstract. Exogenous eicosapentaenoic acid (EPA) and docosahexaenoic acid (DCHA) have been compared with exogenous arachidonic acid for their capacity to modulate the oxidative metabolism of mem-brane-derived arachidonic acid by the 5-lipoxygenase pathway in ionophore-activated human neutrophils and for their suitability as parallel substrates in this pathway. The products from specific 14C- or 3H-labeled substrates were isolated by reverse phase high performance liquid chromatography (RP-HPLC) and were identified by elution of radiolabel at the retention times of the appro-priate synthetic standards. Each product was also char-acterized by its ultraviolet (UV) absorption spectrum, and 7-hydroxy-DCHA was defined in addition by analysis of its mass spectrum. The metabolites, 5-hy-droxyeicosatetraenoic acid, leukotriene B4 (LTB4), 6-trans-LTB4 diastereoisomers, 5-hydroxyeicosapentae-noic acid, 6-trans-leukotriene B5 diastereoisomers, leu-kotriene B5 (LTB5), and 7-hydroxy-DCHA were quan-titated by integrated UV absorbance during resolution by RP-HPLC. LTB4 and LTB5 were also quantitated by Dr. Lee is a recipient of a Saltwell Research Fellowship from the Royal College of Physicians, London. Dr. Mencia-Huerta is a Research Fellow of the Institut National de la Sante et de la Recherche M~dicale, France, and partly supported by the Ministere de l'Industrie et de l