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Journal of Lipid Research, Vol 36, 2590-2598, Copyright © 1995 by Lipid Research, Inc.
WS Powell, S Gravel and F Gravelle
We recently showed that human neutrophils convert arachidonic acid to its
5-oxo metabolite, 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo- ETE).
5-Oxo-ETE, which is synthesized by oxidation of 5-hydroxy-
6,8,11,14-eicosatetraenoic acid (5-HETE) by a highly specific microsomal
dehydrogenase, is a potent stimulator of human neutrophils and eosinophils.
The objective of the current investigation was to determine whether
neutrophils can convert 5,8,11,14,17-eicosapentaenoic acid (EPA) to its
5-oxo metabolite, 5-oxo-6,8,11,14,17-eicosapentaenoic acid (5-oxo-EPE) and,
if so, to compare the biological activities of 5- oxo-EPE and 5-oxo-ETE.
The two major eicosanoids formed by neutrophils incubated with EPA in the
presence of A23187 were 5-hydroxy- 6,8,11,14,17-eicosapentaenoic acid
(5-HEPE) and 5-oxo-EPE. Smaller amounts of LTB5 and 20-hydroxy-LTB5 were
also formed. Phorbol myristate acetate stimulated the formation of
5-oxo-EPE from both EPA and 5-HEPE. 5-HEPE and 5-HETE were equally good
substrates for 5-hydroxyeicosanoid dehydrogenase (Km, ca. 0.85 microM;
Vmax, ca. 1.4 pmol/min per microgram protein). 5-Oxo-EPE mobilized calcium
in neutrophils with an EC50 of 36 nM, about 10 times higher than that of
5-oxo-ETE. 5-Oxo-EPE was also about one-tenth as active as 5-oxo-ETE in
stimulating the migration of both human neutrophils and human eosinophils.
It is concluded that 5-oxo-EPE is readily formed from EPA via 5-HEPE.
However, it is only about one-tenth as potent as 5-oxo-ETE in stimulating
human neutrophils and eosinophils. These results support the contention
that EPA can alleviate certain inflammatory diseases by reducing the
contribution of arachidonate-derived eicosanoids.
ARTICLES
Formation of a 5-oxo metabolite of 5,8,11,14,17-eicosapentaenoic acid and its effects on human neutrophils and eosinophils
Department of Medicine, McGill University, Montreal, Quebec, Canada.
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