Expression of ACE2 in airways: Implication for COVID-19 risk and disease management in patients with chronic inflammatory respiratory diseases

Abstract

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a rising international cause of morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS-CoV-2 and suggested to be a limiting factor for viral entry at the initial infection stage. Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2. The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID-19 risk and affect the management of primary airway diseases. In this review, we focus on the cutting-edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID-19. We also discuss the management of airway diseases, including asthma, COPD, allergic rhinitis, and rhinosinusitis in the era of COVID-19.

Keywords: airway disease; angiotensin-converting enzyme 2; coronavirus disease 2019; management; severe acute respiratory syndrome coronavirus 2.

FIGURE 1

Expression and role of angiotensin‐converting enzyme 2 (ACE2) in airways. ACE2 is expressed in airways, with a particularly higher expression level in nasal epithelial cells and type II alveolar epithelial cells in the lung. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binds to ACE2 expressed on human airway epithelial cells, and then, the serine protease TMPRSS2 cleaves and activates the spike protein of SARS‐CoV‐2, which ultimately facilities virus‐cell fusion and cell entry. As a peptidase, ACE2 catalyses and inactivates angiotensin (Ang) II and produces the vasodilator peptide Ang (1‐7). Ang II induces bronchoconstriction, vasoconstriction, fibroproliferation, cytokine expression, and cell apoptosis, thus promoting tissue injury. Accordingly, ACE2 has protective effects against tissue injury, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), fibrosis, chronic obstructive pulmonary disease (COPD), and allergic asthma

FIGURE 2

Regulation of angiotensin‐converting enzyme 2 (ACE2) expression in airway epithelial cells. Tobacco exposure promotes ACE2 expression in airway epithelial cells, which may associate with increased ACE2 expression in the lung of patients with chronic obstructive pulmonary disease (COPD). Interferon (IFN)‐α and IFN‐γ promote ACE2 expression in airway epithelial cells. Allergens and interleukin (IL)‐13 inhibit ACE2 expression in airway epithelial cells, may account for the lower ACE2 expression in patients with allergic asthma. Varied ACE2 in distinct chronic inflammatory airway diseases may contribute to different susceptibilities to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection