Where are Angiotensin-Converting Enzyme 2 (ACE2) receptors primarily located in the lungs?

From the Guidelines

Angiotensin-Converting Enzyme 2 (ACE2) receptors in the lungs are primarily located on the surface of alveolar epithelial type II cells, which are found in the alveoli of the lower respiratory tract. These receptors are also present on bronchial epithelial cells, pulmonary endothelial cells, and alveolar macrophages, but their concentration is highest in the alveolar region 1. ACE2 receptors serve an important physiological function by converting angiotensin II to angiotensin 1-7, helping to regulate blood pressure and fluid balance. Their location in the alveoli is particularly significant because these air sacs are responsible for oxygen and carbon dioxide exchange. This distribution explains why respiratory infections that target ACE2 receptors, such as SARS-CoV-2, often cause damage to the alveoli, leading to impaired gas exchange and potentially severe respiratory complications. The abundance of these receptors in the lower respiratory tract contributes to the pathophysiology of COVID-19 pneumonia and acute respiratory distress syndrome in severe cases. Key points to consider include:

• The alveolar epithelium and capillary endothelium express ACE2 1
• ACE2 receptors are also found on vascular endothelial cells, pericytes, cardiomyocytes, and macrophages 1
• The location of ACE2 receptors in the lungs is critical to understanding the pathophysiology of COVID-19 and other respiratory infections that target these receptors. Given the evidence, the primary location of ACE2 receptors in the lungs is on alveolar epithelial type II cells, which is crucial for understanding the impact of SARS-CoV-2 infection on the lower respiratory tract 1.

From the Research

Location of ACE2 Receptors in the Lungs

• ACE2 receptors are found in various cells in the lungs, including:
  • Alveolar type II (ATII) cells, which are the main source of surfactant 2
  • Alveolar macrophages 3
• These receptors are predominantly observed in the alveolated parenchyma of the lungs 3
• The expression of ACE2 in the lungs is increased with age, particularly in patients requiring mechanical ventilation, and is associated with prominent expression in ATII cells 3
• The ACE2 receptor plays a crucial role in the pathogenesis of COVID-19, as it is the primary receptor used by SARS-CoV-2 to enter host cells 4, 5, 6

Cell-Specific Expression of ACE2

• ATII cells express ACE2, which allows SARS-CoV-2 to enter and infect these cells, leading to damage and potentially severe consequences, including injury to the alveolar-capillary barrier, lung edema, and inflammation 2, 3
• Alveolar macrophages also express ACE2, which may contribute to the immune response to SARS-CoV-2 infection 3

Clinical Implications

• Understanding the location and expression of ACE2 receptors in the lungs is important for developing effective treatments for COVID-19, particularly those targeting the ACE2 receptor or the renin-angiotensin-aldosterone system (RAAS) 4, 5, 6