Interactions Between 5-Oxo-Ete and Chemokines in Stimulating Eosinophils
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 potentI. 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.
KeywordsHuman Neutrophil Actin Polymerization Calcium Mobilization Phorbol Myristate Acetate Potent Stimulator
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