共 43 条
Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide
被引:92
作者:
Reber, Laurent L.
[1
,2
,8
,10
]
Gillis, Caitlin M.
[8
,10
]
Starkl, Philipp
[1
,2
,11
,12
]
Joensson, Friederike
[8
,10
]
Sibilano, Riccardo
[1
,2
]
Marichal, Thomas
[1
,2
,13
,14
]
Gaudenzio, Nicolas
[1
,2
]
Berard, Marion
[9
]
Rogalla, Stephan
[3
,4
]
Contag, Christopher H.
[3
,4
,5
,6
,7
]
Bruhns, Pierre
[8
,10
]
Galli, Stephen J.
[1
,2
,5
]
机构:
[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Sean N Parker Ctr Allergy & Asthma Res, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Pediat, Div Neonatol, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Stanford, CA 94305 USA
[5] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[6] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA
[7] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA
[8] Inst Pasteur, Dept Immunol, Unit Antibodies Therapy & Pathol, F-75015 Paris, France
[9] Inst Pasteur, Anim Cent, F-75015 Paris, France
[10] INSERM, U1222, F-75015 Paris, France
[11] Med Univ Vienna, Austrian Acad Sci, Res Ctr Mol Med, CeMM, A-1090 Vienna, Austria
[12] Med Univ Vienna, Dept Med 1, Res Lab Infect Biol, A-1090 Vienna, Austria
[13] Univ Liege, GIGA Res, B-4000 Liege, Belgium
[14] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium
基金:
美国国家卫生研究院;
欧盟地平线“2020”;
欧洲研究理事会;
奥地利科学基金会;
关键词:
RECRUITMENT;
INFLAMMATION;
CELLS;
MICE;
LY6G;
ACTIVATION;
D O I:
10.1084/jem.20161238
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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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页码:1249 / 1258
页数:10
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