Extracellular histones are clinically relevant mediators in the pathogenesis of acute respiratory distress syndrome.
Extracellular histones are clinically relevant mediators in the pathogenesis of acute respiratory distress syndrome.
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细胞外组蛋白是急性呼吸窘迫综合征发病机制中的临床相关介质
DOI：
10.1186/s12931-017-0651-5
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发表时间：
2017-09-02
影响因子：
5.8
通讯作者：
Wen Z
中科院分区：
文献类型：
--
作者：
Lv X;Wen T;Song J;Xie D;Wu L;Jiang X;Jiang P;Wen Z
最近，细胞外组蛋白被确定为参与各种器官损伤发病机制的炎症介质。本研究旨在检查急性呼吸窘迫综合征（ARDS）患者的细胞外组蛋白水平及其临床意义，并通过离体研究探索组蛋白介导的作用。获得了 96 名 ARDS 患者和 30 名健康志愿者的细胞外组蛋白、细胞因子谱和临床数据。将人支气管上皮细胞（BEAS-2B）、人肺动脉内皮细胞（HPAEC）和人单核细胞U937细胞暴露于从ARDS患者收集的支气管肺泡灌洗液（BALF）中，并评估细胞损伤和细胞因子产生。此外，还评估了肝素或抗组蛋白抗体进行组蛋白靶向干预的效果。 ARDS 患者的血浆和 BALF 细胞外组蛋白水平远高于健康对照。细胞外组蛋白与 ARDS 严重程度和死亡率之间存在显着相关性。此外，细胞外组蛋白与 ARDS 患者中检测到的明显全身炎症相关。离体分析进一步表明，ARDS患者的BALF显着诱导上皮细胞和内皮细胞损伤，并刺激U937细胞上清液中细胞因子的产生。对这些细胞的不利影响可以通过肝素或抗组蛋白抗体消除。 ARDS 患者的细胞外组蛋白过度增加，可能通过诱导细胞损伤和促进全身炎症而导致疾病恶化。靶向细胞外组蛋白可能为治疗 ARDS 提供一种有前景的方法。本文的在线版本 (10.1186/s12931-017-0651-5) 包含补充材料，可供授权用户使用。
Extracellular 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. Extracellular 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. Plasma 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. Extracellular 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. The online version of this article (10.1186/s12931-017-0651-5) contains supplementary material, which is available to authorized users.
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影响因子：
6.7
作者：
Westman J;Papareddy P;Dahlgren MW;Chakrakodi B;Norrby-Teglund A;Smeds E;Linder A;Mörgelin M;Johansson-Lindbom B;Egesten A;Herwald H
通讯作者：
Herwald H
影响因子：
9
作者：
Silk E;Zhao H;Weng H;Ma D
通讯作者：
Ma D
DOI：
10.1016/j.trsl.2015.04.015
发表时间：
2016-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Standiford TJ;Ward PA
通讯作者：
Ward PA
影响因子：
8.8
作者：
Alhamdi, Yasir;Zi, Min;Toh, Cheng-Hock
通讯作者：
Toh, Cheng-Hock
影响因子：
5.6
作者：
Umbrello M;Formenti P;Bolgiaghi L;Chiumello D
通讯作者：
Chiumello D