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Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide
Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection o...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413333/ https://www.ncbi.nlm.nih.gov/pubmed/28385925 http://dx.doi.org/10.1084/jem.20161238 |
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author | Reber, Laurent L. Gillis, Caitlin M. Starkl, Philipp Jönsson, Friederike Sibilano, Riccardo Marichal, Thomas Gaudenzio, Nicolas Bérard, Marion Rogalla, Stephan Contag, Christopher H. Bruhns, Pierre Galli, Stephen J. |
author_facet | Reber, Laurent L. Gillis, Caitlin M. Starkl, Philipp Jönsson, Friederike Sibilano, Riccardo Marichal, Thomas Gaudenzio, Nicolas Bérard, Marion Rogalla, Stephan Contag, Christopher H. Bruhns, Pierre Galli, Stephen J. |
author_sort | Reber, Laurent L. |
collection | PubMed |
description | Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection of diphtheria toxin induces selective neutrophil ablation. Using this model, we found, surprisingly, that neutrophils serve to protect the host from LPS-induced lethal inflammation. This protective role was observed in conventional and germ-free animal facilities, indicating that it does not depend on a particular microbiological environment. Blockade or genetic deletion of myeloperoxidase (MPO), a key neutrophil enzyme, significantly increased mortality after LPS challenge, and adoptive transfer experiments confirmed that neutrophil-derived MPO contributes importantly to protection from endotoxemia. Our findings imply that, in addition to their well-established antimicrobial properties, neutrophils can contribute to optimal host protection by limiting the extent of endotoxin-induced inflammation in an MPO-dependent manner. |
format | Online Article Text |
id | pubmed-5413333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54133332017-11-01 Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide Reber, Laurent L. Gillis, Caitlin M. Starkl, Philipp Jönsson, Friederike Sibilano, Riccardo Marichal, Thomas Gaudenzio, Nicolas Bérard, Marion Rogalla, Stephan Contag, Christopher H. Bruhns, Pierre Galli, Stephen J. J Exp Med Research Articles Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection of diphtheria toxin induces selective neutrophil ablation. Using this model, we found, surprisingly, that neutrophils serve to protect the host from LPS-induced lethal inflammation. This protective role was observed in conventional and germ-free animal facilities, indicating that it does not depend on a particular microbiological environment. Blockade or genetic deletion of myeloperoxidase (MPO), a key neutrophil enzyme, significantly increased mortality after LPS challenge, and adoptive transfer experiments confirmed that neutrophil-derived MPO contributes importantly to protection from endotoxemia. Our findings imply that, in addition to their well-established antimicrobial properties, neutrophils can contribute to optimal host protection by limiting the extent of endotoxin-induced inflammation in an MPO-dependent manner. The Rockefeller University Press 2017-05-01 /pmc/articles/PMC5413333/ /pubmed/28385925 http://dx.doi.org/10.1084/jem.20161238 Text en © 2017 Reber et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Reber, Laurent L. Gillis, Caitlin M. Starkl, Philipp Jönsson, Friederike Sibilano, Riccardo Marichal, Thomas Gaudenzio, Nicolas Bérard, Marion Rogalla, Stephan Contag, Christopher H. Bruhns, Pierre Galli, Stephen J. Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title | Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title_full | Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title_fullStr | Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title_full_unstemmed | Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title_short | Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
title_sort | neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413333/ https://www.ncbi.nlm.nih.gov/pubmed/28385925 http://dx.doi.org/10.1084/jem.20161238 |
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