We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury.
- Authors
Wu, Meng-Li; Liu, Feng-Liang; Sun, Jing; Li, Xin; He, Xiao-Yan; Zheng, Hong-Yi; Zhou, Yan-Heng; Yan, Qihong; Chen, Ling; Yu, Guo-Ying; Chang, Junbiao; Jin, Xia; Zhao, Jincun; Chen, Xin-Wen; Zheng, Yong-Tang; Wang, Jian-Hua
- Abstract
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.A schematic illustration of SARS-CoV-2 triggers MC rapid degranulation to induce alveolar epithelial inflammation and lung injury. SARS-CoV-2 triggers an immediate mast cell (MC) degranulation, which initiates the alveolar epithelial inflammation and disrupts the tight junction. MC stabilizers that block degranulation reduce virus-induced lung inflammation and injury.
- Publication
Signal Transduction & Targeted Therapy, 2021, Vol 6, Issue 1, p1
- ISSN
2095-9907
- Publication type
Article
- DOI
10.1038/s41392-021-00849-0