title: 5-oxo-ETE is a major oxidative stress-induced arachidonate metabolite in B lymphocytes.
abstract: B lymphocytes convert arachidonic acid (AA) to the 5-lipoxygenase products leukotriene B4 (LTB4) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) when subjected to oxidative stress. 5-HETE has little biological activity, but can be oxidized by a selective dehydrogenase in some cells to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemoattractant. We found that CESS cells, a B lymphocyte cell line, convert AA to 5-oxo-ETE and this is selectively stimulated by oxidative stress. In the presence of H2O2, 5-oxo-ETE is a major AA metabolite in these cells (5-oxo-ETE≈5-HETE>LTB4). The cyclooxygenase product 12-hydroxy-5,8,10-heptadecatrienoic acid is also formed, but is not affected by H2O2. Diamide had effects similar to those of H2O2 and both substances had similar effects on human tonsillar B cells. H2O2 also stimulated 5-oxo-ETE formation from its direct precursor 5-HETE in tonsillar B and CESS cells, and this was inhibited by the glutathione reductase inhibitor carmustine. H2O2 concomitantly induced rapid increases in GSSG and NADP+ and reductions in GSH and NADPH. We conclude that oxidative stress stimulates 5-oxo-ETE synthesis in B lymphocytes by two mechanisms: activation of 5-lipoxygenase and increased oxidation of 5-HETE by NADP+-dependent 5-hydroxyeicosanoid dehydrogenase. B lymphocyte-derived 5-oxo-ETE could contribute to eosinophilic inflammation in asthma and other allergic diseases.
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC, Canada H2X 2P2.
authors.forename: Gail E
authors.initials: GE
authors.lastname: Grant
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gravel
authors.forename: Julie
authors.initials: J
authors.lastname: Guay
authors.forename: Pranav
authors.initials: P
authors.lastname: Patel
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Mazer
authors.forename: Joshua
authors.initials: J
authors.lastname: Rokach
authors.forename: William S
authors.initials: WS
authors.lastname: Powell
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D016718:Arachidonic Acid; D000001:Calcimycin; D006861:Hydrogen Peroxide; D001094:Arachidonate 5-Lipoxygenase; D005978:Glutathione