Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome

作者：Yanlin Zhang, Jian Zhao, Li Guan, Lijun Mao, Shuqiang Li, Jinyuan Zhao · 发表于：Journal of Occupational Medicine and Toxicology · 年份：2020 · DOI：10.1186/s12995-020-00282-z · 被引用次数：11 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Immune Response and Inflammation、S100 Proteins and Annexins

Abstract Background Chlorine gas (Cl 2 ) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl 2 is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl 2 -induced ARDS. Methods ARDS was induced by Cl 2 exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury (ALI). Histone H4 or anti-H4 antibody was administered through the tail vein 1 h prior to Cl 2 exposure to study the pathogenic role of histone H4. Toll-like receptor 2 knock-out ( Tlr2 -KO) and Tlr4 -KO mice were used in conjunction with blocking antibody against TLR1, TLR2, TLR4, or TLR6 to explore the mechanism involved in histone H4-mediated injury. Results Cl 2 exposure induced a concentration-dependent ALI. The levels of circulating histone H4 were positively correlated with Cl 2 concentrations. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration, while anti-H4 antibody showed protective effects. Tlr4 deficiency improved lethality rate, blood gas, and pulmonary edema, and pr...