Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

TLDR

SARS is an acute respiratory disease, and the receptor ACE2—whose protein expression across organs is largely unknown—has been identified as the functional entry point for SARS‑CoV. The study aimed to map ACE2 protein distribution across human tissues to elucidate potential SARS‑CoV entry routes. The authors performed immunohistochemical localization of ACE2 protein in a broad panel of human organs. The study found that ACE2 protein is highly expressed on lung alveolar epithelial cells, small intestinal enterocytes, and vascular endothelial and smooth muscle cells, suggesting these tissues as primary SARS‑CoV entry routes and helping explain the disease’s clinical manifestations.

Abstract

Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations.