• Xumao Tang, Qian Yu, Xiaoting Wen, Di Qi, Jiao Peng, Jing He, Wang Deng, Tao Zhu, Yan Zhao, and Daoxin Wang.
• Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
• Shock. 2020 Jul 1; 54 (1): 110-118.

BackgroundAcute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high mortality rate, and few effective therapies have been found in the past 50 years, indicating that the pathogenesis of ARDS remains unclear. Exosomes, a novel cross-communication mechanism, are involved in critical diseases. However, the role of circulating exosomes in the development of ARDS remains poorly understood.MethodsIn the present study, naive mice were treated with circulating exosomes from lipopolysaccharide (LPS)-induced ARDS mice or exosome-depleted serum. Histological lung damage, bronchoalveolar lavage fluid (BALF), and endoplasmic reticulum (ER) stress were measured.ResultsIncreased tumor necrosis factor (TNF)-α, interleukin (IL)-6, total cell counts, polymorphonuclear (PMN) leukocyte proportions and myeloperoxidase (MPO) activity in BALF, and increased wet/dry weight ratios and protein concentrations in BALF were found in mice after exosome injection but not in mice treated with exosome-depleted serum. Furthermore, western blot analysis showed that circulating exosomes from ARDS mice upregulated glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression and downregulated β-Catenin and VE-cadherin expression in lung tissues.ConclusionsCollectively, these data demonstrate that circulating exosomes from LPS-induced ARDS mice trigger ER stress in lung tissue, facilitating the development of ARDS, at least partly by promoting endothelial dysfunction.

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