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
✍ Scribed by L. Iversen; K. Fogh; K. Kragballe
- Publisher
- Springer-Verlag
- Year
- 1992
- Tongue
- English
- Weight
- 478 KB
- Volume
- 284
- Category
- Article
- ISSN
- 0340-3696
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✦ Synopsis
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 ~tM) 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 PGE 2 formation, but at similar concentrations there was a dose-dependent decrease in LTB 4 formation (ICso = 45.0 ltM). The inhibition of LTB 4 formation by DGLA was associated with a dosedependent increase in its 15-LO metabolite 15-hydroxyeicosatrienoic acid (15-HETrE) and its CO metabolite prostaglandin E 1 (PGE1). Incubation of HPLM with 15-HETrE (0-1.5 pM) alone did not result in a change in PGE 2 formation, whereas 15-HETrE was a much more potent inhibitor of LTB 4 formation (ICso = 0.5 ltM) than DGLA. These results show that the addition of DGLA to HPML results in a selective inhibition of LTB 4 formation, presumably via its metabolite (15-HETrE).