1. Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease.
- Author
-
Yang Peng, Zhao-Ni Wang, Shi-Ying Chen, Ai-Ru Xu, Zhang-Fu Fang, Jing Sun, Zi-Qing Zhou, Xiao-Tao Hou, Lai-Jian Cen, Jian-Juan Ma, Jin-Cun Zhao, Wei-Jie Guan, De-Yun Wang, and Nan-Shan Zhong
- Subjects
- *
CHRONIC obstructive pulmonary disease , *LUNGS , *ANGIOTENSIN converting enzyme , *POSITIVE pressure ventilation , *COVID-19 , *SARS-CoV-2 - 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 nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive 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-positive club cells in COPD patients than in nonsmokers. 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 coexisting COPD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF