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.
引用
收藏
页码:1249 / 1258
页数:10
相关论文
共 43 条
[1]   Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice [J].
Abram, Clare L. ;
Roberge, Gray L. ;
Hu, Yongmei ;
Lowell, Clifford A. .
JOURNAL OF IMMUNOLOGICAL METHODS, 2014, 408 :89-100
[2]   Distinct Roles for Neutrophils and Dendritic Cells in Inflammation and Autoimmunity in motheaten Mice [J].
Abram, Clare L. ;
Roberge, Gray L. ;
Pao, Lily I. ;
Neel, Benjamin G. ;
Lowell, Clifford A. .
IMMUNITY, 2013, 38 (03) :489-501
[3]   Neutrophils, from Marrow to Microbes [J].
Borregaard, Niels .
IMMUNITY, 2010, 33 (05) :657-670
[4]   A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration [J].
Buch, T ;
Heppner, FL ;
Tertilt, C ;
Heinen, TJAJ ;
Kremer, M ;
Wunderlich, FT ;
Jung, S ;
Waisman, A .
NATURE METHODS, 2005, 2 (06) :419-426
[5]   NEUTROPHILS ARE ESSENTIAL FOR EARLY ANTI-LISTERIA DEFENSE IN THE LIVER, BUT NOT IN THE SPLEEN OR PERITONEAL-CAVITY, AS REVEALED BY A GRANULOCYTE-DEPLETING MONOCLONAL-ANTIBODY [J].
CONLAN, JW ;
NORTH, RJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (01) :259-268
[6]   Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice [J].
Daley, Jean M. ;
Thomay, Alan A. ;
Connolly, Michael D. ;
Reichner, Jonathan S. ;
Albina, Jorge E. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2008, 83 (01) :64-70
[7]   Marked alterations of neutrophil functions during sepsis-induced immunosuppression [J].
Demaret, Julie ;
Venet, Fabienne ;
Friggeri, Arnaud ;
Cazalis, Marie-Angelique ;
Plassais, Jonathan ;
Jallades, Laurent ;
Malcus, Christophe ;
Poitevin-Later, Francoise ;
Textoris, Julien ;
Lepape, Alain ;
Monneret, Guillaume .
JOURNAL OF LEUKOCYTE BIOLOGY, 2015, 98 (06) :1081-1090
[8]   Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation [J].
El Kebir, Driss ;
Jozsef, Levente ;
Pan, Wanling ;
Filep, Janos G. .
CIRCULATION RESEARCH, 2008, 103 (04) :352-359
[9]   Deletion of Syk in Neutrophils Prevents Immune Complex Arthritis [J].
Elliott, Emily R. ;
Van Ziffle, Jessica A. ;
Scapini, Patrizia ;
Sullivan, Brandon M. ;
Locksley, Richard M. ;
Lowell, Clifford A. .
JOURNAL OF IMMUNOLOGY, 2011, 187 (08) :4319-4330
[10]   Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF [J].
Fadok, VA ;
Bratton, DL ;
Konowal, A ;
Freed, PW ;
Westcott, JY ;
Henson, PM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (04) :890-898