ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma.
COVID-19
SARS-CoV-2
bronchial asthma
chronic obstructive pulmonary disease
coronavirus disease
pandemic
viral infections
Journal
Respirology (Carlton, Vic.)
ISSN: 1440-1843
Titre abrégé: Respirology
Pays: Australia
ID NLM: 9616368
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
10
11
2020
received:
05
08
2020
accepted:
06
12
2020
pubmed:
18
1
2021
medline:
18
5
2021
entrez:
17
1
2021
Statut:
ppublish
Résumé
COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
Sections du résumé
BACKGROUND AND OBJECTIVE
COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD.
METHODS
We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.
RESULTS
Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients.
CONCLUSION
Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
Identifiants
pubmed: 33455043
doi: 10.1111/resp.14003
pmc: PMC8014151
doi:
Substances chimiques
Peptidyl-Dipeptidase A
EC 3.4.15.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
442-451Subventions
Organisme : Hunter Medical Research Institute
Organisme : National Health and Medical Research Council
ID : 1079187
Organisme : National Health and Medical Research Council
ID : 1175134
Organisme : SPHERE
Organisme : Rebecca L. Cooper Medical Research Foundation
Organisme : Clifford Craig Foundation Launceston General Hospital
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 Asian Pacific Society of Respirology.
Références
Emerg Infect Dis. 2020 Jul;26(7):1470-1477
pubmed: 32255761
Am J Respir Crit Care Med. 2020 Jul 1;202(1):83-90
pubmed: 32348692
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
J Allergy Clin Immunol. 2021 Feb;147(2):510-519.e5
pubmed: 33068560
J Allergy Clin Immunol. 2020 Jul;146(1):80-88.e8
pubmed: 32422146
N Engl J Med. 2020 Mar 19;382(12):1177-1179
pubmed: 32074444
Eur Respir J. 2020 May 14;55(5):
pubmed: 32269089
J Clin Virol. 2016 Jun;79:68-73
pubmed: 27105315
Sci China Life Sci. 2020 Mar;63(3):364-374
pubmed: 32048163
J Allergy Clin Immunol. 2020 Jul;146(1):203-206.e3
pubmed: 32333915
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Crit Care. 2020 Mar 18;24(1):108
pubmed: 32188484
JAMA. 2020 Apr 28;323(16):1574-1581
pubmed: 32250385
Respirology. 2021 May;26(5):442-451
pubmed: 33455043
Biostat Bioinforma Biomath. 2013 Aug;3(3):71-85
pubmed: 25558171
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
Pharmacol Ther. 2008 Mar;117(3):313-53
pubmed: 18234348
Antiviral Res. 2010 Mar;85(3):551-5
pubmed: 19995578
J Gen Virol. 2012 Sep;93(Pt 9):1924-1929
pubmed: 22718567
Travel Med Infect Dis. 2020 Mar - Apr;34:101623
pubmed: 32179124
J Biol Chem. 2012 Mar 9;287(11):8457-67
pubmed: 22253445
J Clin Med. 2020 Mar 20;9(3):
pubmed: 32244852
J Biol Chem. 2018 Jul 27;293(30):11709-11726
pubmed: 29887526
Lancet Infect Dis. 2020 May;20(5):533-534
pubmed: 32087114
Mol Ther Methods Clin Dev. 2020 May 22;18:1-6
pubmed: 32537478
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7809-14
pubmed: 18490652
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734
pubmed: 32376634
J Mol Cell Cardiol. 2014 Jan;66:167-76
pubmed: 24332999
Signal Transduct Target Ther. 2020 Dec 4;5(1):283
pubmed: 33277466
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Eur Respir J. 2020 May 14;55(5):
pubmed: 32217650
Nat Med. 2005 Aug;11(8):875-9
pubmed: 16007097
Am J Respir Crit Care Med. 2020 Jul 1;202(1):8-10
pubmed: 32437628
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Respir Res. 2007 Jul 09;8:51
pubmed: 17620132
Int J Oral Sci. 2020 Feb 24;12(1):8
pubmed: 32094336
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L84-96
pubmed: 19411314
J Virol. 2011 Dec;85(24):13363-72
pubmed: 21994442
Am J Physiol Lung Cell Mol Physiol. 2015 Feb 15;308(4):L325-43
pubmed: 25480335
bioRxiv. 2020 Jul 13;:
pubmed: 32511382
Nat Med. 2020 May;26(5):681-687
pubmed: 32327758
Eur Respir J. 2020 May 7;55(5):
pubmed: 32269088
Life Sci Alliance. 2020 Jul 23;3(9):
pubmed: 32703818
J Allergy Clin Immunol. 2020 Jul;146(1):208-211
pubmed: 32450087