SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury  

作　　者：Meng-Li Wu Feng-Liang Liu Jing Sun Xin Li Xiao-Yan He Hong-Yi Zheng Yan-Heng Zhou Qihong Yan Ling Chen Guo-Ying Yu Junbiao Chang Xia Jin Jincun Zhao Xin-Wen Chen Yong-Tang Zheng Jian-Hua Wang 

机构地区：[1]College of Life Science,Henan Normal University,Xinxiang 453007,China [2]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China [3]State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510182,China [4]Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [5]Bioland Laboratory,Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Guangzhou 510005,China [6]Shanghai Public Health Clinical Center Affiliated to Fudan University,Shanghai 201508,China [7]University of Chinese Academy of Sciences,Beijing 100039,China

出　　处：《Signal Transduction and Targeted Therapy》2022年第1期295-309,共15页信号转导与靶向治疗（英文）

摘　　要：SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity.Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments.Mast cells(MCs)are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.In this study,we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury.SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques,and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells;MC degranulation altered various signaling pathways in alveolar epithelial cells,particularly,the induction of pro-inflammatory factors and consequential disruption of tight junctions.Importantly,the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury.These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation,and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.

关 键 词：INFLAMMATION LUNG ALVEOLAR 

分 类 号：R563[医药卫生—呼吸系统]