Effect of dihomogammalinolenic acid and its 15-lipoxygenase metabolite on eicosanoid metabolism by human mononuclear leukocytes in vitro: selective inhibition of the 5-lipoxygenase pathway

Abstract

The purpose of the present study was to determine the effect of the n-6 fatty acid, dihomogammalinolenic acid (DGLA, 20∶3, n-6) on arachidonic acid (AA) (C20∶4) metabolism by human peripheral mononuclear leukocytes (HPML). After incubation of HPML with A23187 (5 ΜM) and DGLA, the cyclooxygenase (CO) and lipoxygenase (LO) products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) combined with radioimmunoassay. DGLA led to no change in PGE₂ formation, but at similar concentrations there was a dose-dependent decrease in LTB₄ formation (IC₅₀=45.0 ΜM). The inhibition of LTB₄ formation by DGLA was associated with a dosedependent increase in its 15-LO metabolite 15-hydroxyeicosatrienoic acid (15-HETrE) and its CO metabolite prostaglandin E₁ (PGE₁). Incubation of HPLM with 15-HETrE (0–1.5 ΜM) alone did not result in a change in PGE₂ formation, whereas 15-HETrE was a much more potent inhibitor of LTB₄ formation (IC₅₀=0.5 ΜM) than DGLA. These results show that the addition of DGLA to HPML results in a selective inhibition of LTB₄ formation, presumably via its metabolite (15-HETrE).