Little to no expression of angiotensin‐converting enzyme‐2 on most human peripheral blood immune cells but highly expressed on tissue macrophages
Open accessAbstract
Angiotensin‐converting enzyme‐2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood‐derived immune cells including CD4+ T, CD8+ T, activated CD4+/CD8+ T, Tregs, Th17, NKT, B, NK cells, monocytes, dendritic cells, and granulocytes. There was no ACE2 expression on platelets and very low level of ACE2 protein expression on the surface of human primary pulmonary alveolar epithelial cells. The ACE2 expression was markedly upregulated on the activated type 1 macrophages (M1). Immunohistochemistry demonstrated high expressions of ACE2 on human tissue macrophages, such as alveolar macrophages, Kupffer cells within livers, and microglial cells in brain at steady state. The data suggest that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS‐CoV‐2 infection and therefore need to be considered for the prevention and treatment of COVID‐19.
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ACE2 is expressed primarily on activated tissue macrophages but not on peripheral blood mononuclear cells in healthy people.
“In a study examining the prevalence of ACE2 on immune cells, it was found to be expressed primarily on activated tissue macrophages but not on peripheral blood mononuclear cells in healthy people.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [28]
Section 3.5 reports high ACE2 expression on tissue macrophages from normal adult donors, while Section 3.4 reports increased expression on activated M1 macrophages generated from blood monocytes. The paper does not establish that the tissue macrophages were activated. Its PBMC results report little to no ACE2 expression on most immune-cell types from healthy donors, rather than none on all PBMCs; page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredACE2, TMPRSS2, NRP1, integrins, and cathepsins are also expressed on mast cells.
“ACE2, TMPRSS2, NRP1, integrins, and cathepsins are also expressed on mast cells (Figure 1), 28,29”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [28]
The Introduction discusses ACE2, TMPRSS2 and cathepsin B/L as possible SARS-CoV-2 entry factors, while section 3.5 reports ACE2 expression on tissue macrophages. Neither passage addresses their expression on mast cells, and a search for mast cells found no relevant passage. The copy therefore cannot verify the claim about ACE2, TMPRSS2, NRP1, integrins and cathepsins on mast cells. (LLM, conf=0.76)
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- Authors
- Song, X., Hu, W., Yu, H., Zhao, L., Zhao, Y., Zhao, X., Xue, H., & Zhao, Y.
- Affiliations
- Hackensack Meridian Health (US)
- Tianhe Stem Cell Biotechnologies Inc. Paramus New Jersey USA
- Corresponding author
- Zhao, Yong
- Venue
- Cytometry Part A
- Publisher
- Wiley
- Published
- 2020-12-16
- Volume
- 103
- Issue
- 2
- Pages
- 136-145
- ISSN
- 1552-4922 (ISSN-L)
- 1552-4930
- OpenAlex
- W3113115015
- Cited by
- 117
- References
- 30
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 15 · 2023: 27 · 2022: 33 · 2021: 28 · 2020: 2
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cytometry Part A (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- angiotensin-converting enzyme 2, ACE2 expression, SARS-CoV-2, COVID-19 pandemic, tissue macrophages, alveolar macrophages, Kupffer cells, microglia, peripheral immune cells, T cells, dendritic cells, platelets, alveolar epithelial cells, M1 macrophages, viral receptor
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Angiotensins, Humans, Peptidyl-Dipeptidase A, Macrophages, Alveolar
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