Extracellular Histones Are Mediators of Death through TLR2 and TLR4 in Mouse Fatal Liver Injury

被引：425

作者：

Xu, Jun ^{[1
]}

Zhang, Xiaomei ^{[2
]}

Monestier, Marc ^{[3
,4
]}

Esmon, Naomi L. ^{[1
]}

Esmon, Charles T. ^{[1
,2
,5
,6
]}

机构：

[1] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA

[2] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[3] Temple Univ, Sch Med, Temple Autoimmun Ctr, Philadelphia, PA 19140 USA

[4] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA

[5] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA

[6] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA

来源：

JOURNAL OF IMMUNOLOGY | 2011年 / 187卷 / 05期

基金：

美国国家卫生研究院;

关键词：

TOLL-LIKE RECEPTOR-2; TRAUMA PATIENTS; PLASMA DNA; SEPSIS; MICE; HEPATOTOXICITY; INFLAMMATION; NUCLEOSOMES; COAGULATION; RESPONSES;

D O I：

10.4049/jimmunol.1003930

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We previously reported that extracellular histones are major mediators of death in sepsis. Infusion of extracellular histones leads to increased cytokine levels. Histones activate TLR2 and TLR4 in a process that is enhanced by binding to DNA. Activation of TLR4 is responsible for the histone-dependent increase in cytokine levels. To study the impact of histone release on pathology we used two models: a Con A-triggered activation of T cells to mimic sterile inflammation, and acetaminophen to model drug-induced tissue toxicity. Histones were released in both models and anti-histone Abs were protective. TLR2- or TLR4-null mice were also protected. These studies imply that histone release contributes to death in inflammatory injury and in chemical-induced cellular injury, both of which are mediated in part through the TLRs. The Journal of Immunology, 2011, 187: 2626-2631.

引用

页码：2626 / 2631

页数：6

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