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


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.

SUBMITTER: Reber LL 

PROVIDER: S-EPMC5413333 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Reber Laurent L LL   Gillis Caitlin M CM   Starkl Philipp P   Jönsson Friederike F   Sibilano Riccardo R   Marichal Thomas T   Gaudenzio Nicolas N   Bérard Marion M   Rogalla Stephan S   Contag Christopher H CH   Bruhns Pierre P   Galli Stephen J SJ  

The Journal of experimental medicine 20170406 5


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, <i>PMN<sup>DTR</sup></i> 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. Thi  ...[more]

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