Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection.
Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection.
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DOI：
10.3390/pathogens10050509
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发表时间：
2021-04-23
期刊：
影响因子：
--
通讯作者：
Gong B
中科院分区：
文献类型：
--
作者：
Liu Y;Garron TM;Chang Q;Su Z;Zhou C;Qiu Y;Gong EC;Zheng J;Yin YW;Ksiazek T;Brasel T;Jin Y;Boor P;Comer JE;Gong B
SARS-CoV-2大流行激发了人们对理解感染后急性呼吸窘迫综合征（ARDS）基本病理学的新兴趣。然而，SRAS-CoV-2感染后ARDS的发病机制在很大程度上仍然未知。在本研究中，我们以细胞类型的方式，包括1型和2型肺泡细胞和血管内皮细胞（EC），巨噬细胞和T细胞，检测了COVID-19患者死后肺切片和SARS-CoV-2感染的非人灵长类动物模型肺组织中的细胞凋亡。多靶点免疫荧光分析和蛋白质印迹法表明，在SARS-CoV-2感染过程中，内源性和外源性凋亡途径都被激活。此外，我们观察到SARS-CoV-2不能诱导人支气管上皮细胞凋亡（即，BEAS 2B细胞）和原代人脐静脉内皮细胞（HUVEC），其对SARS-CoV-2感染是难治的。然而，用SARS-CoV-2感染共培养的Vero细胞和HUVECs或Vero细胞和BEAS 2B细胞诱导Vero细胞和HUVECs/BEAS 2B细胞的凋亡，但不改变HUVECs或BEAS 2B细胞对病毒的容许性。暴露后处理Vero细胞和HUVEC的共培养物与一种新的非环核苷酸小分子EPAC 1特异性激活剂减少HUVEC的凋亡。这些发现可能有助于描绘一个新的见解ARDS的发病机制后，SARS-CoV-2感染。
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.
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影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
20.3
作者：
Bombeli, T;Karsan, A;Harlan, JM
通讯作者：
Harlan, JM
DOI：
10.1016/j.brainresprot.2004.04.001
发表时间：
2004-08-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Daniel, B;DeCoster, MA
通讯作者：
DeCoster, MA
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
32.4
作者：
Hoagland DA;Møller R;Uhl SA;Oishi K;Frere J;Golynker I;Horiuchi S;Panis M;Blanco-Melo D;Sachs D;Arkun K;Lim JK;tenOever BR
通讯作者：
tenOever BR