5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors.

Abstract

Stmamary 5-Lipoxygenase activation of human blood polymorphonudear cells (PMN) from asthmatic patients (asthmatics) was studied to investigate whether differences may exist with healthy subjects (controls). The respective cell capacities to produce lipoxins (LXs), leukotrienes, and 5(S),15(S)-dihydroxyeicosatetraenoic acid [5(S),15(S)-diHETE] were compared under in vitro stimulation by ionophore A23187, with or without exogenous 15(S)-hydoxyeicosatetraenoic acid [15(S)-HETE]. Eicosanoids were analyzed by elution with an isocratic reverse-phase high performance liquid chromatography system, and their profiles, detected by simultaneous monitoring at 302, 280, and 246 nm, were evaluated on the basis of chromatographic behavior: UV spectral characteristics and coelution with synthetic standards. In the presence of exogenous 15(S)-HETE, human PMN were able to produce LXs and 5(S),15(S)-diHETE. Moreover, the total amount of LXs biosynthesized by PMN from asthmatics was twofold higher than that biosynthesized by PMN from controls. In the absence of exogenous 15(S)-HETE, PMN from asthmatics were able to produce 5(S),15(S)-diHETE, and LXs from endogenous sources, whereas in the same experimental conditions, no detectable amounts of these compounds were released by PMN from controls. The levels of 5(S),15(S)-diHETE, and LXs biosynthesized from endogenous arachidonic acid were highly correlated. Two different LX patterns were observed involving two possible metabolic pathways: (a) via the intermediate 5,6-epoxytetraene alone for LXs generation from exogenous 15(S)-HETE; and (b) via 5,6-and/or 14,15-epoxytetraenes leading to the formation of an enzyme-bound delocalized carbocation for LXs generation from endogenous arachidonate, respectively. The enhanced 5-lipoxygenase activation of blood PMN from asthmatics and the metabolism of exogenous 15(S)-HETE may reflect a priming induced by various mediators released from environmental cells, and could be considered as a model of transcellular signalization between PMN and endothelial cells.

Novel oxylipins formed from docosahexaenoic acid by potato lipoxygenase—10(S)‐hydroxydocosahexaenoic acid and 10,20‐dihydroxydocosahexaenoic acid

“…Both forms seem to coexist in equilibrium, which depends on the ability of the solvent to form hydrogen bonds with the hydroxyl groups of 7,17-and 10,20-diHDHA. It is noteworthy that a similarly split spectrum (with a secondary maximum at 226 nm and a primary maximum at 243 nm) was previously described for an arachidonic acid metabolite formed by double lipoxygenation (5,15-dihydroxyeicosatetraenoic acid) (21)(22)(23)(24)(25)(26), although no explanation for it was provided.…”

Reduced 15-lipoxygenase 2 and lipoxin A4/leukotriene B4ratio in children with cystic fibrosis

“…LXA 4 is biosynthesised in the respiratory tract by transcellular cooperation of neutrophils [19], eosinophils [20], alveolar macrophages [21] or airway epithelial cells [22], each expressing different lipoxygenase (LO) enzymes ( fig. 1) [2,23].…”

Lipoxin and resolvin biosynthesis is dependent on 5‐lipoxygenase activating protein

“…LXs can be formed via 2 routes ( Fig. 1), either neutrophil-derived 5-LO/platelet 12-LO (4-6) or 15-LO/5-LO (7,8). For Rv biosynthesis, only the latter pathway could be confirmed (9).…”