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Leukotriene B 4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid‐stimulated neutrophils
Author(s) -
Serezani Carlos H. C.,
Aronoff David M.,
Jancar Sonia,
PetersGolden Marc
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1004587
Subject(s) - nadph oxidase , arachidonic acid , linoleic acid , leukotriene b4 , polyunsaturated fatty acid , biology , biochemistry , nicotinamide adenine dinucleotide phosphate , oxidase test , arachidonate 5 lipoxygenase , stimulation , lipoxygenase , superoxide , leukotriene , phosphorylation , lipid signaling , respiratory burst , receptor , fatty acid , enzyme , inflammation , endocrinology , immunology , asthma
Polyunsaturated fatty acids (PUFAs) and leukotriene B 4 (LTB 4 ) are involved in many inflammatory and physiological conditions. The role of arachidonic acid (AA) and linoleic acid (LA) in promoting the assembly of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits is well known, but the involvement of LTB 4 and other 5‐lipoxygenase (5‐LO) pathway metabolites of AA in hydrogen peroxide (H 2 O 2 ) production by PUFA‐stimulated polymorphonuclear leukocytes (PMNs) has not been investigated. We examined this question by determining H 2 O 2 production as well as phosphorylation and membrane translocation of the p47phox subunit of NADPH oxidase. Elicited peritoneal PMNs from rats and from 5‐LO‐deficient or wild‐type mice were pretreated with or without inhibitors of LT biosynthesis and antagonists of the receptors for LTB 4 and cysteinyl LTs for 20 min before stimulation with AA (at 5 and 20 μM) or LA (at 20 μM). PUFAs elicited H 2 O 2 production in a dose‐dependent manner, and pharmacologic or genetic inhibition of LT synthesis decreased H 2 O 2 production by ∼40% when compared with untreated controls. LTB 4 was the moiety responsible for H 2 O 2 production, as revealed by studies using receptor antagonists and its exogenous addition. LTB 4 itself also promoted p47phox phosphorylation and translocation. These results identify a heretofore unrecognized role for activation of 5‐LO and subsequent production of LTB 4 in stimulation of PMN NADPH oxidase activation by PUFAs.