|Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome|
|Zhang, Yanlin1; Wen, Zongmei2; Guan, Li1; Jiang, Ping3; Gu, Tao4; Zhao, Jinyuan1; Lv, Xin2; Wen, Tao5|
|WOS标题词||Science & Technology|
|关键词[WOS]||ACUTE LUNG INJURY ; LIVER-INJURY ; CIRCULATING NUCLEOSOMES ; THROMBIN GENERATION ; MICE ; HEPARIN ; SEPSIS ; MEDIATORS ; BINDING ; TLR4|
Background: Systemic 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.
Methods: The 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.
Results: Extracellular 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).
Conclusion: Extracellular 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.
|项目编号||81272142 ; 81372094 ; 81400052 ; 14ZR1434400 ; 14PJD030|
|资助机构||National Natural Science Foundation of China, Beijing, People&prime ; s Republic of China ; Beijing Municipal Health System High-level Talent Training Project, Beijing, People&prime ; s Republic of China ; Shanghai Municipal Committee of Science and Technology, Shanghai, People&prime ; s Republic of China ; Pujiang Talent Program, Shanghai, People&prime ; s Republic of China|
|作者单位||1.Peking Univ, Res Ctr Occupat Med, Hosp 3, Beijing 100871, Peoples R China|
2.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Anesthesiol, Shanghai 200092, Peoples R China
3.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Emergency, Shanghai 200092, Peoples R China
4.First Hosp Qinhuangdao, Dept Oncol, Qinhuangdao, Hebei Province, Peoples R China
5.Capital Med Univ, Beijing Youan Hosp, Beijing Inst Hepatol, Beijing 100069, Peoples R China
|Zhang, Yanlin,Wen, Zongmei,Guan, Li,et al. Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome[J]. ANESTHESIOLOGY,2015,122(1):127-139.|
|APA||Zhang, Yanlin.,Wen, Zongmei.,Guan, Li.,Jiang, Ping.,Gu, Tao.,...&Wen, Tao.(2015).Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome.ANESTHESIOLOGY,122(1),127-139.|
|MLA||Zhang, Yanlin,et al."Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome".ANESTHESIOLOGY 122.1(2015):127-139.|