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Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF

Microvascular plasma protein leakage is an essential component of the inflammatory response and serves an important function in local host defense and tissue repair. Mediators such as histamine and bradykinin act directly on venules to increase the permeability of endothelial cell (EC) junctions. Ne...

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Autores principales: Finsterbusch, Michaela, Voisin, Mathieu-Benoit, Beyrau, Martina, Williams, Timothy John, Nourshargh, Sussan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076577/
https://www.ncbi.nlm.nih.gov/pubmed/24913232
http://dx.doi.org/10.1084/jem.20132413
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author Finsterbusch, Michaela
Voisin, Mathieu-Benoit
Beyrau, Martina
Williams, Timothy John
Nourshargh, Sussan
author_facet Finsterbusch, Michaela
Voisin, Mathieu-Benoit
Beyrau, Martina
Williams, Timothy John
Nourshargh, Sussan
author_sort Finsterbusch, Michaela
collection PubMed
description Microvascular plasma protein leakage is an essential component of the inflammatory response and serves an important function in local host defense and tissue repair. Mediators such as histamine and bradykinin act directly on venules to increase the permeability of endothelial cell (EC) junctions. Neutrophil chemoattractants also induce leakage, a response that is dependent on neutrophil adhesion to ECs, but the underlying mechanism has proved elusive. Through application of confocal intravital microscopy to the mouse cremaster muscle, we show that neutrophils responding to chemoattractants release TNF when in close proximity of EC junctions. In vitro, neutrophils adherent to ICAM-1 or ICAM-2 rapidly released TNF in response to LTB(4), C5a, and KC. Further, in TNFR(−/−) mice, neutrophils accumulated normally in response to chemoattractants administered to the cremaster muscle or dorsal skin, but neutrophil-dependent plasma protein leakage was abolished. Similar results were obtained in chimeric mice deficient in leukocyte TNF. A locally injected TNF blocking antibody was also able to inhibit neutrophil-dependent plasma leakage, but had no effect on the response induced by bradykinin. The results suggest that TNF mediates neutrophil-dependent microvascular leakage. This mechanism may contribute to the effects of TNF inhibitors in inflammatory diseases and indicates possible applications in life-threatening acute edema.
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spelling pubmed-40765772014-12-30 Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF Finsterbusch, Michaela Voisin, Mathieu-Benoit Beyrau, Martina Williams, Timothy John Nourshargh, Sussan J Exp Med Brief Definitive Report Microvascular plasma protein leakage is an essential component of the inflammatory response and serves an important function in local host defense and tissue repair. Mediators such as histamine and bradykinin act directly on venules to increase the permeability of endothelial cell (EC) junctions. Neutrophil chemoattractants also induce leakage, a response that is dependent on neutrophil adhesion to ECs, but the underlying mechanism has proved elusive. Through application of confocal intravital microscopy to the mouse cremaster muscle, we show that neutrophils responding to chemoattractants release TNF when in close proximity of EC junctions. In vitro, neutrophils adherent to ICAM-1 or ICAM-2 rapidly released TNF in response to LTB(4), C5a, and KC. Further, in TNFR(−/−) mice, neutrophils accumulated normally in response to chemoattractants administered to the cremaster muscle or dorsal skin, but neutrophil-dependent plasma protein leakage was abolished. Similar results were obtained in chimeric mice deficient in leukocyte TNF. A locally injected TNF blocking antibody was also able to inhibit neutrophil-dependent plasma leakage, but had no effect on the response induced by bradykinin. The results suggest that TNF mediates neutrophil-dependent microvascular leakage. This mechanism may contribute to the effects of TNF inhibitors in inflammatory diseases and indicates possible applications in life-threatening acute edema. The Rockefeller University Press 2014-06-30 /pmc/articles/PMC4076577/ /pubmed/24913232 http://dx.doi.org/10.1084/jem.20132413 Text en © 2014 Finsterbusch 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Finsterbusch, Michaela
Voisin, Mathieu-Benoit
Beyrau, Martina
Williams, Timothy John
Nourshargh, Sussan
Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title_full Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title_fullStr Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title_full_unstemmed Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title_short Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
title_sort neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of tnf
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076577/
https://www.ncbi.nlm.nih.gov/pubmed/24913232
http://dx.doi.org/10.1084/jem.20132413
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