The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in postmortem lung sections from COVID-19 patients and in lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence assays and Western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with a novel non-cyclic nucleotide small molecule EPAC1-specific activator reduced apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.
【저자키워드】 SARS-CoV-2, Apoptosis, Human, lung, non-human primate, Endothelial cell, epithelial cell, co-culture, TUNEL assay, 【초록키워드】 Treatment, pathology, ARDS, Pathogenesis, macrophages, T cells, SARS-COV-2 infection, SARS-CoV-2 pandemic, Infection, virus, cells, immunofluorescence assay, non-human primate model, SRAS-CoV-2, acute respiratory distress, nucleotide, COVID-19 patient, syndrome, help, lung tissue, western blotting, Vero Cell, Alter, vascular endothelial cell, Cell, intrinsic, examined, reduced, activated, alveolar cell, induce, bronchial epithelial cell, co-cultured, extrinsic apoptotic pathway, umbilical,