Extracellular histones are clinically relevant mediators in the pathogenesis of acute respiratory distress syndrome

Respiratory Research

Research

Jiong Song¹  Zongmei Wen¹  Xin Lv¹  Xuemei Jiang¹  Ping Jiang²  Liang Wu³  Dong Xie³  Tao Wen⁴ 

[1] Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, People’s Republic of China;Department of Emergency, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, People’s Republic of China;Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, People’s Republic of China;Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, People’s Republic of China;

关键词: Acute respiratory distress syndrome (ARDS);    Extracellular histones;    Cell damage;    Systemic inflammation;   

DOI  :  10.1186/s12931-017-0651-5

 received in 2017-05-17, accepted in 2017-08-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundExtracellular histones were recently identified as an inflammatory mediator involved in the pathogenesis of various organ injuries. This study aimed to examine extracellular histone levels and their clinical implications in acute respiratory distress syndrome (ARDS) patients and to explore histone-mediated effects through ex-vivo investigations.MethodsExtracellular histones, cytokine profiles and clinical data from 96 ARDS patients and 30 healthy volunteers were obtained. Human bronchial epithelial cells (BEAS-2B), human pulmonary artery endothelial cells (HPAEC), and human monocytic U937 cells were exposed to bronchoalveolar lavage fluid (BALF) collected from ARDS patients, and cellular damage and cytokine production were assessed. Furthermore, the effect of histone-targeted interventions by heparin or anti-histone antibody was evaluated.ResultsPlasma and BALF extracellular histone levels were much higher in ARDS patients than in healthy controls. There was a significant association between extracellular histones and ARDS severity and mortality. In addition, extracellular histones correlated with an evident systemic inflammation detected in ARDS patients. Ex-vivo analysis further showed that ARDS patient’s BALF remarkably induced epithelial and endothelial cell damage and stimulated cytokine production in the supernatant of U937 cells. The adverse effects on these cells could be abrogated by heparin or anti-histone antibody.ConclusionsExtracellular histones in ARDS patients are excessively increased and may contribute to disease aggravation by inducing cellular damage and promoting systemic inflammation. Targeting extracellular histones may provide a promising approach for treating ARDS.

【 授权许可】

CC BY   
© The Author(s). 2017