Interactions Between 5-Oxo-Ete and Chemokines in Stimulating Eosinophils

Abstract

Cells containing 5-lipoxygenase convert arachidonic to both LTA₄-derived leukotrienes and 5-HETE (Fig. 1). Although 5-HETE has biological effects on inflammatory cells that are not mediated by LT receptors, it is not very potent^I. However, 5-HETE is enzymatically oxidized to a product, 5-oxo-ETE, that is 100-fold more potent than its precursor in activating neutrophils². The enzyme responsible for the formation of 5-oxo-ETE, 5-hydroxyeicosanoid dehydrogenase, is highly specific for eicosanoids containing a 5S-hydroxyl group followed by a6-transdouble bond³. Thus 5S-HETE is its preferred substrate, whereas LTB₄, 5R-HETE, and other HETEs undergo little or no metabolism³. The high degree of specificity exhibited by this enzyme was the first clue that its product, 5-oxo-ETE, may serve some biological function. 5Hydroxyeicosanoid dehydrogenase is present in a variety of leukocytes, including neutrophils³, eosinophils⁴, monocytes, and lymphocytes. However, formation of 5-oxoETE depends not only on the presence of this enzyme, but also requires adequate levels of the cofactor NADP^{+ 5}. Thus resting neutrophils are not very active in converting 5HETE to 5-oxo-ETE, whereas neutrophils that have been stimulated to undergo the oxidativburst by addition of phorbol myristate acetate or opsonized zymosan produce substantial amounts of 5-oxo-ETE due to the activation of NADPH oxidase.