Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease

作者：Peng, Yang; Wang, Zhao-Ni; Chen, Shi-Ying; Xu, Ai-Ru; Fang, Zhang-Fu; Sun, Jing; Zhou, Zi-Qing; Hou, Xiao-Tao; Cen, Lai-Jian; Ma, Jian-Juan; Zhao, Jin-Cun; Guan, Wei-Jie^*; Wang, De-Yun^*; Zhong, Nan-Shan^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2022, 322(5): L712-L721.

DOI：10.1152/ajplung.00305.2021

• ACE2
• club cell
• COPD
• in vitro
• SARS-CoV-2

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.

• 单位
  广州医学院; 1; 南方医科大学