• Yanlin Zhang, Zongmei Wen, Li Guan, Ping Jiang, Tao Gu, Jinyuan Zhao, Xin Lv, and Tao Wen.
• From the Research Center of Occupational Medicine, Peking University Third Hospital, Beijing, People's Republic of China (Y.Z., L.G., J.Z.); Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China (Z.W., X.L.); Department of Emergency, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China (P.J.); Department of Oncology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei Province, People's Republic of China (T.G.); and Beijing Institute of Hepatology, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, People's Republic of China (T.W.).
• Anesthesiology. 2015 Jan 1;122(1):127-39.

BackgroundSystemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS.MethodsThe authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration.ResultsExtracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14).ConclusionExtracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.

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