HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print July 8, 2005

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1004587v1 78/4/976    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Serezani, C. H. C. Articles by Peters-Golden, M. Search for Related Content PubMed PubMed Citation Articles by Serezani, C. H. C. Articles by Peters-Golden, M.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1004587

Received for publication October 14, 2004.
Revised May 26, 2005.
Accepted for publication June 6, 2005.

Article

Leukotriene B₄ mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils

Carlos H. C. Serezani ^*, David M. Aronoff ^*, Sonia Jancar , and Marc Peters-Golden ^*@

Divisions of Infectious Diseases and *Pulmonary and Critical Care Medicine, Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor; and Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, Brazil

^@ To whom correspondence should be addressed. E-mail: petersm{at}umich.edu.

	Abstract

Polyunsaturated fatty acids (PUFAs) and leukotriene B₄ (LTB₄) 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 LTB₄ and other 5-lipoxygenase (5-LO) pathway metabolites of AA in hydrogen peroxide (H₂O₂) production by PUFA-stimulated polymorphonuclear leukocytes (PMNs) has not been investigated. We examined this question by determining H₂O₂ 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 LTB₄ and cysteinyl LTs for 20 min before stimulation with AA (at 5 and 20 µM) or LA (at 20 µM). PUFAs elicited H₂O₂ production in a dose-dependent manner, and pharmacologic or genetic inhibition of LT synthesis decreased H₂O₂ production by 40% when compared with untreated controls. LTB₄ was the moiety responsible for H₂O₂ production, as revealed by studies using receptor antagonists and its exogenous addition. LTB₄ itself also promoted p47phox phosphorylation and translocation. These results identify a heretofore unrecognized role for activation of 5-LO and subsequent production of LTB₄ in stimulation of PMN NADPH oxidase activation by PUFAs.

Key Words: PMN • PUFAs • lipid mediators • NADPH oxidase • BLT1

This article has been cited by other articles:

				S. P. Lee, C. H. Serezani, A. I. Medeiros, M. N. Ballinger, and M. Peters-Golden Crosstalk between Prostaglandin E2 and Leukotriene B4 Regulates Phagocytosis in Alveolar Macrophages via Combinatorial Effects on Cyclic AMP J. Immunol., January 1, 2009; 182(1): 530 - 537. [Abstract] [Full Text] [PDF]

				R. A. Gubitosi-Klug, R. Talahalli, Y. Du, J. L. Nadler, and T. S. Kern 5-Lipoxygenase, but Not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy Diabetes, May 1, 2008; 57(5): 1387 - 1393. [Abstract] [Full Text] [PDF]

				E. J. Swindle, J. W. Coleman, F. R. DeLeo, and D. D. Metcalfe Fc{epsilon}RI- and Fc{gamma} Receptor-Mediated Production of Reactive Oxygen Species by Mast Cells Is Lipoxygenase- and Cyclooxygenase-Dependent and NADPH Oxidase-Independent J. Immunol., November 15, 2007; 179(10): 7059 - 7071. [Abstract] [Full Text] [PDF]