Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide.

Reber, LL; Gillis, CM; Starkl, P; Jönsson, F; Sibilano, R; Marichal, T; Gaudenzio, N; Bérard, M; Rogalla, S; Contag, CH; Bruhns, P; Galli, SJ

Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide.

Reber, LL Gillis, CM Starkl, P Jönsson, F Sibilano, R Marichal, T Gaudenzio, N Bérard, M Rogalla, S Contag, CH Bruhns, P Galli, SJ

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Publisher:: Rockefeller University Press
Publication Type:: Journal Article
Citation:: Journal of Experimental Medicine, 2017, 214, (5), pp. 1249-1258
Issue Date:: 2017-05-01

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Field	Value	Language
dc.contributor.author	Reber, LL
dc.contributor.author	Gillis, CM
dc.contributor.author	Starkl, P
dc.contributor.author	Jönsson, F
dc.contributor.author	Sibilano, R
dc.contributor.author	Marichal, T
dc.contributor.author	Gaudenzio, N
dc.contributor.author	Bérard, M
dc.contributor.author	Rogalla, S
dc.contributor.author	Contag, CH
dc.contributor.author	Bruhns, P
dc.contributor.author	Galli, SJ
dc.date.accessioned	2022-08-31T02:23:45Z
dc.date.available	2017-03-01
dc.date.available	2022-08-31T02:23:45Z
dc.date.issued	2017-05-01
dc.identifier.citation	Journal of Experimental Medicine, 2017, 214, (5), pp. 1249-1258
dc.identifier.issn	0022-1007
dc.identifier.issn	1540-9538
dc.identifier.uri	http://hdl.handle.net/10453/161125
dc.description.abstract	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, PMNDTR 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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Rockefeller University Press
dc.relation.ispartof	Journal of Experimental Medicine
dc.relation.isbasedon	10.1084/jem.20161238
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Immunology
dc.subject.mesh	Animals
dc.subject.mesh	Antibodies
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endotoxemia
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Mice
dc.subject.mesh	Neutrophils
dc.subject.mesh	Peroxidase
dc.subject.mesh	Sepsis
dc.subject.mesh	Animals
dc.subject.mesh	Antibodies
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endotoxemia
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Mice
dc.subject.mesh	Neutrophils
dc.subject.mesh	Peroxidase
dc.subject.mesh	Sepsis
dc.subject.mesh	Neutrophils
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Sepsis
dc.subject.mesh	Endotoxemia
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Peroxidase
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Antibodies
dc.title	Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide.
dc.type	Journal Article
utslib.citation.volume	214
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-08-31T02:23:42Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	214
utslib.citation.issue	5

Abstract:

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, PMNDTR 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.

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http://hdl.handle.net/10453/161125