Synthesis, biological effects and pathophysiological implications of the novel arachidonic acid metabolite 5-oxo-eicosatetraenoic acid (Review). 1998

Zimpfer, and Hofmann, and Dichmann, and Schopf, and Norgauer
Departments of clinical and experimental dermatology, University of Freiburg, Freiburg, Germany.

Arachidonic acid is rapidly metabolized by several distinct enzymes including the 5-lipoxygenase generating leukotrienes and 5-hydroxyeicosatetraenoic acid (5-HETE). These well studied metabolites cause a variety of physiological and pathophysiological effects in different tissues. Recently, oxidation of 5-HETE to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) by an NADP+-dependent dehydrogenase has been demonstrated. Calcium ionophors and protein kinase C activators stimulate the synthesis of 5-oxo-ETE in neutrophils, eosinophils and monocytes. This novel arachidonic acid metabolite has a potent chemotactic activity for neutrophils and eosinophils. It stimulates adhesion of neutrophils and induces reactive oxygen metabolites in eosinophils. There is evidence that 5-oxo-ETE and 5-HETE interact with a specific G-protein coupled receptor. Since in contrast to 5-oxo-ETE much higher concentrations of 5-HETE are needed to provoke cell responses, 5-oxo-ETE might be the physiological relevant ligand for this putative receptor. Further downstream signalling pathways of this ligand include calcium transients, actin polymerization, activation of phosphatidylinositol-3-kinase and MAP-kinase. 5-oxo-ETE has been extracted from scales of psoriatic patients and injection of 5-oxo-ETE into rabbit subcutis causes a severe edema with an inflammatory cell infiltrate resembling an urticarial lesion. These findings indicate, that 5-oxo-ETE might play a role in different cutaneous inflammatory diseases.

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