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Title: Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease
Authors: Peng, Y
Zhao-Ni Wang
Chen, SY
Xu, AR
Fang, ZF
Sun, J
Zhou, ZQ
Hou, XT
Cen, LJ
Ma, JJ
Zhao, JC
Guan, WJ
Wang, DY 
Zhong, NS
Keywords: ACE2
club cell
in vitro
Angiotensin-Converting Enzyme 2
Epithelial Cells
Peptidyl-Dipeptidase A
Pulmonary Disease, Chronic Obstructive
Issue Date: 1-May-2022
Publisher: American Physiological Society
Citation: Peng, Y, Zhao-Ni Wang, Chen, SY, Xu, AR, Fang, ZF, Sun, J, Zhou, ZQ, Hou, XT, Cen, LJ, Ma, JJ, Zhao, JC, Guan, WJ, Wang, DY, Zhong, NS (2022-05-01). Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease. American Journal of Physiology - Lung Cellular and Molecular Physiology 322 (5) : L712-L721. ScholarBank@NUS Repository.
Abstract: Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with non-smokers, the median percentage of club cells in bronchiolar epithelium and ACE2+ club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2+ club cells in COPD patients than in non-smokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with co-existing COPD.
Source Title: American Journal of Physiology - Lung Cellular and Molecular Physiology
ISSN: 1040-0605
DOI: 10.1152/AJPLUNG.00305.2021
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