Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Usi...

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Main Authors:	Chen, Mei, Lam, Bing K., Kanaoka, Yoshihide, Nigrovic, Peter A., Audoly, Laurent P., Austen, K. Frank, Lee, David M.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118292/

id	pubmed-2118292
recordtype	oai_dc
spelling	pubmed-21182922007-12-13 Neutrophil-derived leukotriene B4 is required for inflammatory arthritis Chen, Mei Lam, Bing K. Kanaoka, Yoshihide Nigrovic, Peter A. Audoly, Laurent P. Austen, K. Frank Lee, David M. Brief Definitive Reports Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption. The Rockefeller University Press 2006-04-17 /pmc/articles/PMC2118292/ /pubmed/16567388 http://dx.doi.org/10.1084/jem.20052371 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Mei Lam, Bing K. Kanaoka, Yoshihide Nigrovic, Peter A. Audoly, Laurent P. Austen, K. Frank Lee, David M.
spellingShingle	Chen, Mei Lam, Bing K. Kanaoka, Yoshihide Nigrovic, Peter A. Audoly, Laurent P. Austen, K. Frank Lee, David M. Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
author_facet	Chen, Mei Lam, Bing K. Kanaoka, Yoshihide Nigrovic, Peter A. Audoly, Laurent P. Austen, K. Frank Lee, David M.
author_sort	Chen, Mei
title	Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
title_short	Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
title_full	Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
title_fullStr	Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
title_full_unstemmed	Neutrophil-derived leukotriene B4 is required for inflammatory arthritis
title_sort	neutrophil-derived leukotriene b4 is required for inflammatory arthritis
description	Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118292/
_version_	1611414673117151232

Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

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