Cargando…

Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis

Angiotensin converting enzyme 2 (ACE2) is the putative functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current literature on the abundance and distribution of ACE2 protein in the human respiratory tract is controversial. We examined the effect of age and lung in...

Descripción completa

Detalles Bibliográficos
Autores principales: Soni, Sourabh, Jiang, Yujie, Tesfaigzi, Yohannes, Hornick, Jason L., Çataltepe, Sule
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904186/
https://www.ncbi.nlm.nih.gov/pubmed/33626084
http://dx.doi.org/10.1371/journal.pone.0247510
_version_ 1783654879006294016
author Soni, Sourabh
Jiang, Yujie
Tesfaigzi, Yohannes
Hornick, Jason L.
Çataltepe, Sule
author_facet Soni, Sourabh
Jiang, Yujie
Tesfaigzi, Yohannes
Hornick, Jason L.
Çataltepe, Sule
author_sort Soni, Sourabh
collection PubMed
description Angiotensin converting enzyme 2 (ACE2) is the putative functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current literature on the abundance and distribution of ACE2 protein in the human respiratory tract is controversial. We examined the effect of age and lung injury on ACE2 protein expression in rodent and non-human primate (NHP) models. We also examined ACE2 expression in human tissues with and without coronavirus disease 19 (COVID-19). ACE2 expression was detected at very low levels in preterm, but was absent in full-term and adult NHP lung homogenates. This pattern of ACE2 expression contrasted with that of transmembrane protease serine type 2 (TMPRSS2), which was significantly increased in full-term newborn and adult NHP lungs compared to preterm NHP lungs. ACE2 expression was not detected in NHP lungs with cigarette smoke-induced airway disease or bronchopulmonary dysplasia. Murine lungs lacked basal ACE2 immunoreactivity, but responded to hyperoxia, bacterial infection, and allergen exposure with new ACE2 expression in bronchial epithelial cells. In human specimens, robust ACE2 immunoreactivity was detected in ciliated epithelial cells in paranasal sinus specimens, while ACE2 expression was detected only in rare type 2 alveolar epithelial cells in control lungs. In autopsy specimens from patients with COVID-19 pneumonia, ACE2 was detected in rare ciliated epithelial and endothelial cells in the trachea, but not in the lung. There was robust expression of ACE2 expression in F344/N rat nasal mucosa and lung specimens, which authentically recapitulated the ACE2 expression pattern in human paranasal sinus specimens. Thus, ACE2 protein expression demonstrates a significant gradient between upper and lower respiratory tract in humans and is scarce in the lung. This pattern of ACE2 expression supports the notion of sinonasal epithelium being the main entry site for SARS-CoV-2 but raises further questions on the pathogenesis and cellular targets of SARS-CoV-2 in COVID-19 pneumonia.
format Online
Article
Text
id pubmed-7904186
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-79041862021-03-02 Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis Soni, Sourabh Jiang, Yujie Tesfaigzi, Yohannes Hornick, Jason L. Çataltepe, Sule PLoS One Research Article Angiotensin converting enzyme 2 (ACE2) is the putative functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current literature on the abundance and distribution of ACE2 protein in the human respiratory tract is controversial. We examined the effect of age and lung injury on ACE2 protein expression in rodent and non-human primate (NHP) models. We also examined ACE2 expression in human tissues with and without coronavirus disease 19 (COVID-19). ACE2 expression was detected at very low levels in preterm, but was absent in full-term and adult NHP lung homogenates. This pattern of ACE2 expression contrasted with that of transmembrane protease serine type 2 (TMPRSS2), which was significantly increased in full-term newborn and adult NHP lungs compared to preterm NHP lungs. ACE2 expression was not detected in NHP lungs with cigarette smoke-induced airway disease or bronchopulmonary dysplasia. Murine lungs lacked basal ACE2 immunoreactivity, but responded to hyperoxia, bacterial infection, and allergen exposure with new ACE2 expression in bronchial epithelial cells. In human specimens, robust ACE2 immunoreactivity was detected in ciliated epithelial cells in paranasal sinus specimens, while ACE2 expression was detected only in rare type 2 alveolar epithelial cells in control lungs. In autopsy specimens from patients with COVID-19 pneumonia, ACE2 was detected in rare ciliated epithelial and endothelial cells in the trachea, but not in the lung. There was robust expression of ACE2 expression in F344/N rat nasal mucosa and lung specimens, which authentically recapitulated the ACE2 expression pattern in human paranasal sinus specimens. Thus, ACE2 protein expression demonstrates a significant gradient between upper and lower respiratory tract in humans and is scarce in the lung. This pattern of ACE2 expression supports the notion of sinonasal epithelium being the main entry site for SARS-CoV-2 but raises further questions on the pathogenesis and cellular targets of SARS-CoV-2 in COVID-19 pneumonia. Public Library of Science 2021-02-24 /pmc/articles/PMC7904186/ /pubmed/33626084 http://dx.doi.org/10.1371/journal.pone.0247510 Text en © 2021 Soni et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Soni, Sourabh
Jiang, Yujie
Tesfaigzi, Yohannes
Hornick, Jason L.
Çataltepe, Sule
Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title_full Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title_fullStr Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title_full_unstemmed Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title_short Comparative analysis of ACE2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: A conundrum for COVID-19 pathogenesis
title_sort comparative analysis of ace2 protein expression in rodent, non-human primate, and human respiratory tract at baseline and after injury: a conundrum for covid-19 pathogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904186/
https://www.ncbi.nlm.nih.gov/pubmed/33626084
http://dx.doi.org/10.1371/journal.pone.0247510
work_keys_str_mv AT sonisourabh comparativeanalysisoface2proteinexpressioninrodentnonhumanprimateandhumanrespiratorytractatbaselineandafterinjuryaconundrumforcovid19pathogenesis
AT jiangyujie comparativeanalysisoface2proteinexpressioninrodentnonhumanprimateandhumanrespiratorytractatbaselineandafterinjuryaconundrumforcovid19pathogenesis
AT tesfaigziyohannes comparativeanalysisoface2proteinexpressioninrodentnonhumanprimateandhumanrespiratorytractatbaselineandafterinjuryaconundrumforcovid19pathogenesis
AT hornickjasonl comparativeanalysisoface2proteinexpressioninrodentnonhumanprimateandhumanrespiratorytractatbaselineandafterinjuryaconundrumforcovid19pathogenesis
AT cataltepesule comparativeanalysisoface2proteinexpressioninrodentnonhumanprimateandhumanrespiratorytractatbaselineandafterinjuryaconundrumforcovid19pathogenesis