Activation of lung endothelial cells by extracellular histone in mice with acute respiratory distress syndrome
10.3760/cma.j.issn.1001-9391.2019.10.004
- VernacularTitle: 急性呼吸窘迫综合征发病小鼠细胞外组蛋白对肺内皮细胞的激活作用
- Author:
Yanlin ZHANG
1
;
Jian ZHAO
2
;
Li GUAN
1
;
Yimu ZHENG
1
;
Ming CHEN
1
;
Lixia GUO
1
;
Xiaoxu GUAN
1
;
Lijun MAO
1
;
Shuqiang LI
1
;
Jinyuan ZHAO
1
Author Information
1. Research Center of Occupational Medicine, Peking University Third Hospital, Beijing 100191, China
2. Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China
- Publication Type:Journal Article
- Keywords:
Mice;
Endothelial cells;
Extracellular histones;
Acute respiratory distress syndrome;
Inflammation
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2019;37(10):732-736
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) .
Methods:The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model.
Results:The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells.
Conclusion:Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.
