Deficiency of S100A8/A9 attenuates pulmonary microvascular leakage in septic mice

作者全名："Yu, Jiang; Zhao, Boying; Pi, Qiangzhong; Zhou, Guoxiang; Cheng, Zhe; Qu, Can; Wang, Xiaowen; Kong, Lingwen; Luo, Suxin; Du, Dingyuan; Guo, Yongzheng"

作者地址："[Yu, Jiang; Zhou, Guoxiang; Luo, Suxin; Guo, Yongzheng] Chongqing Med Univ, Affiliated Hosp 1, Div Cardiol, Chongqing 400016, Peoples R China; [Zhao, Boying; Kong, Lingwen; Du, Dingyuan] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Dept Cardiothorac Surg, Chongqing 400010, Peoples R China; [Zhao, Boying; Kong, Lingwen; Du, Dingyuan] Chongqing Key Lab Emergency Med, Chongqing 400010, Peoples R China; [Pi, Qiangzhong] Army Mil Med Univ, Southwest Hosp, Dept Resp Med, Chongqing, Peoples R China; [Cheng, Zhe] Chongqing Univ, Gorges Hosp 3, Dept Cardiol, Chongqing 404199, Peoples R China; [Qu, Can] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China; [Wang, Xiaowen] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China"

通信作者："Guo, YZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Div Cardiol, Chongqing 400016, Peoples R China.; Du, DY (通讯作者)，Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Dept Cardiothorac Surg, Chongqing 400010, Peoples R China.; Du, DY (通讯作者)，Chongqing Key Lab Emergency Med, Chongqing 400010, Peoples R China."

来源：RESPIRATORY RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001107543800001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：sepsis; Pulmonary inflammation; Vascular leakage; Acute lung injury

摘要："BackgroundWe have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and sepsis-induced lung damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic value of S100A8/A9 in sepsis.MethodsSepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice through the cecal ligation and puncture (CLP). Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic.ResultsS100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; However, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs.ConclusionThe present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis."

基金机构：N.A.

基金资助正文：N.A.