The DOI matches its Crossref record, with a small difference in title or year; 34 of the 34 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286
COVID-19: consider cytokine storm syndromes and immunosuppression
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30628-0 · Cited by 9,664
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897
Pathological findings of COVID-19 associated with acute respiratory distress syndrome
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30076-x · Cited by 8,545
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
Hamming, I., Timens, W., Bulthuis, M., Lely, A., Navis, G., & van Goor, H. (2004) · The Journal of Pathology · doi:10.1002/path.1570 · Cited by 5,676
Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy
Onder, G., Rezza, G., & Brusaferro, S. (2020) · JAMA · doi:10.1001/jama.2020.4683 · Cited by 4,171
Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Cheng, L., Li, J., Wang, X., Wang, F., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0901-9 · Cited by 2,614
HCA Lung Biological Network, Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., Talavera-López, C., Maatz, H., Reichart, D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0868-6 · Cited by 2,501
Cytokine release syndrome in severe COVID-19
Moore, J. B., & June, C. H. (2020) · Science · doi:10.1126/science.abb8925 · Cited by 1,912
Standardizing immunophenotyping for the Human Immunology Project
Maecker, H. T., McCoy, J. P., & Nussenblatt, R. B. (2012) · Nature reviews. Immunology · doi:10.1038/nri3158 · Cited by 1,199
Sungnak, W., Huang, N., Bécavin, C., & Berg, M. (2020) · PubMed · Cited by 1,196
Ding, Y., He, L., Zhang, Q., Huang, Z., Che, X., Hou, J., Wang, H., Shen, H., Qiu, L., Li, Z., et al. (2004) · The Journal of Pathology · doi:10.1002/path.1560 · Cited by 1,082
The protein expression profile of ACE2 in human tissues
Hikmet, F., Méar, L., Edvinsson, Å., Micke, P., Uhlén, M., & Lindskog, C. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209610 · Cited by 1,016
[A pathological report of three COVID-19 cases by minimal invasive autopsies].
Yao, X. H., Li, T. Y., He, Z. C., Ping, Y. F., Liu, H. W., Yu, S. C., Mou, H. M., Wang, L. H., Zhang, H. R., Fu, W. J., et al. (2020) · PubMed · doi:10.3760/cma.j.cn112151-20200312-00193 · Cited by 963
Jia, H. P., Look, D. C., Shi, L., Hickey, M. A., Pewe, L. L., Netland, J., Farzan, M., Wohlford-Lenane, C., Perlman, S. M., & McCray, P. B. (2005) · Journal of Virology · doi:10.1128/jvi.79.23.14614-14621.2005 · Cited by 956
Single-Cell RNA Expression Profiling of ACE2, the Receptor of SARS-CoV-2
Zhao, Y., Zhao, Z., Wang, Y., Zhou, Y., Ma, Y., & Zuo, W. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202001-0179le · Cited by 916
Self-citationVankadari, N., & Wilce, M. C. J. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1739565 · Cited by 588
A human peripheral blood monocyte-derived subset acts as pluripotent stem cells
Zhao, Y. L., Glesne, D. A., & Huberman, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0536882100 · Cited by 458
Self-citationGeneration of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
Sun, J., Zhuang, Z., Zheng, J. H., Li, K., Wong, R. L.-Y., Liu, D., Huang, J., He, J., Zhu, A., Zhao, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.010 · Cited by 440
CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement
Ulrich, H., & Pillat, M. M. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-09976-7 · Cited by 418
Feng, Z., Diao, B., Wang, R., Wang, G., Wang, C., Tan, Y., Liu, L., Wang, C., Liu, Y., Liu, Y., et al. (2020) · medRxiv · doi:10.1101/2020.03.27.20045427 · Cited by 375
Ural, B. B., Yeung, S. T., Damani‐Yokota, P., Devlin, J. C., de Vries, M., Vera‐Licona, P., Samji, T., Sawai, C. M., Jang, G., Perez, O. A., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aax8756 · Cited by 298
A simple method for the rapid generation of recombinant adenovirus vectors
Anderson, R., Haskell, R. E., Xia, H., Bj, R., & Davidson, B. L. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301197 · Cited by 259
Bertani, F. R., Mozetic, P., Fioramonti, M., Iuliani, M., Ribelli, G., Pantano, F., Santini, D., Tonini, G., Trombetta, M., Businaro, L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-08121-8 · Cited by 244
Small molecule inhibitors of ROR γt: Targeting T h17 cells and other applications
Huh, J. R., & Littman, D. R. (2012) · European Journal of Immunology · doi:10.1002/eji.201242740 · Cited by 174
Kim, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124549 · Cited by 124
Dengue Fever, COVID ‐19 ( SARS‐CoV ‐2), and Antibody‐Dependent Enhancement ( ADE ): A Perspective
Ulrich, H., Pillat, M. M., & Tárnok, A. (2020) · Cytometry Part A · doi:10.1002/cyto.a.24047 · Cited by 122
Zhao, Y. L., Lin, B. J., Darflinger, R. J., Zhang, Y., Holterman, M., & Skidgel, R. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004226 · Cited by 78
Self-citationVankadari, N., & Wilce, J. A. (2020) · Figshare · doi:10.6084/m9.figshare.11993181 · Cited by 67
Zhao, Y. L., Jiang, Z., Delgado, E., Li, H., Zhou, H., Hu, W., Pérez‐Basterrechea, M., Janošťáková, A., Tan, Q., Wang, J., et al. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0078 · Cited by 54
Self-citationReleased Exosomes Contribute to the Immune Modulation of Cord Blood-Derived Stem Cells
Hu, W., Song, X. H., Yu, H., Sun, J., & Zhao, Y. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00165 · Cited by 43
Self-citationYu, H., Hu, W., Song, X. H., & Zhao, Y. L. (2020) · Cells · doi:10.3390/cells9061350 · Cited by 12
Self-citationYu, H., Hu, W., Song, X. H., Descalzi‐Montoya, D. B., Yang, Z. R., Korngold, R., & Zhao, Y. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124249 · Cited by 8
Self-citation
Cited by
Sorted by citations
FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation
Junqueira, C., Crespo, Â. C., Ranjbar, S., de Lacerda, L., Lewandrowski, M., Ingber, J., Parry, B. A., Ravid, S., Clark, S. A., Schrimpf, M. R., et al. (2022) · Nature · doi:10.1038/s41586-022-04702-4 · Cited by 699
Inflammasome activation at the crux of severe COVID-19
Vora, S. M., Lieberman, J., & Wu, H. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00588-x · Cited by 332
Monocytes and Macrophages in COVID-19
Knoll, R., Schultze, J. L., & Schulte-Schrepping, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.720109 · Cited by 279
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection
Synowiec, A., Szczepański, A., Barreto-Durán, E., Lie, L. K., & Pyrć, K. (2021) · Clinical Microbiology Reviews · doi:10.1128/cmr.00133-20 · Cited by 228
COVID-19, Myocarditis and Pericarditis
Fairweather, D., Beetler, D. J., Di Florio, D. N., Musigk, N., Heidecker, B., & Cooper, L. T. (2023) · Circulation Research · doi:10.1161/circresaha.123.321878 · Cited by 194
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
