Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.
Aged
Aged, 80 and over
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Bronchi
COVID-19
/ enzymology
Cell Line, Tumor
Cigarette Smoking
/ metabolism
Female
Humans
Male
Mice
Middle Aged
Patient Acuity
Pulmonary Alveoli
Pulmonary Disease, Chronic Obstructive
/ enzymology
RNA, Messenger
/ metabolism
Respiratory Mucosa
/ metabolism
SARS-CoV-2
/ physiology
Serine Endopeptidases
/ genetics
Smoke
Nicotiana
Virus Replication
Journal
BMC pulmonary medicine
ISSN: 1471-2466
Titre abrégé: BMC Pulm Med
Pays: England
ID NLM: 100968563
Informations de publication
Date de publication:
23 Aug 2021
23 Aug 2021
Historique:
received:
19
04
2021
accepted:
11
08
2021
entrez:
24
8
2021
pubmed:
25
8
2021
medline:
31
8
2021
Statut:
epublish
Résumé
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.
Sections du résumé
BACKGROUND
BACKGROUND
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro.
METHODS
METHODS
We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively.
RESULTS
RESULTS
ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR.
CONCLUSIONS
CONCLUSIONS
ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.
Identifiants
pubmed: 34425811
doi: 10.1186/s12890-021-01639-8
pii: 10.1186/s12890-021-01639-8
pmc: PMC8381712
doi:
Substances chimiques
RNA, Messenger
0
Smoke
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
TMPRSS2 protein, mouse
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
275Subventions
Organisme : NIDDK NIH HHS
ID : R00 DK103126
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL130045
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL091889
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES006694
Pays : United States
Organisme : NIEHS NIH HHS
ID : ES006614
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI126614
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL098112
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM136853
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM136853
Pays : United States
Organisme : NIH HHS
ID : UH3 OD023282
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL056177
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL139054
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009213
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL132523
Pays : United States
Organisme : NIH HHS
ID : UG3 OD023282
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK103126
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL149744
Pays : United States
Organisme : NIDDK NIH HHS
ID : K99 DK103126
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149744
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2021. The Author(s).
Références
J Allergy Clin Immunol. 2021 Feb;147(2):510-519.e5
pubmed: 33068560
Cell. 2020 Jul 23;182(2):429-446.e14
pubmed: 32526206
Biomolecules. 2021 May 26;11(6):
pubmed: 34073591
Cell Stem Cell. 2020 Dec 3;27(6):869-875.e4
pubmed: 33259798
J Mol Neurosci. 2007;33(3):284-93
pubmed: 17952638
Front Cardiovasc Med. 2020 Oct 09;7:585866
pubmed: 33195473
Nature. 2020 Jun;582(7813):561-565
pubmed: 32365353
Am J Respir Crit Care Med. 2011 Oct 1;184(7):796-802
pubmed: 21965015
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
J Med Virol. 2021 Feb;93(2):1045-1056
pubmed: 32749705
Nat Med. 2021 Mar;27(3):546-559
pubmed: 33654293
J Med Virol. 2020 Sep;92(9):1580-1586
pubmed: 32249956
J Clin Invest. 2020 May 1;130(5):2620-2629
pubmed: 32217835
Cell Rep. 2020 Jul 7;32(1):107863
pubmed: 32610043
Am J Respir Crit Care Med. 2020 Jul 15;202(2):219-229
pubmed: 32432483
Eur Respir J. 2020 Jul 16;56(1):
pubmed: 32444400
N Engl J Med. 2020 Jun 18;382(25):2441-2448
pubmed: 32356628
Eur Respir J. 2020 Aug 20;56(2):
pubmed: 32675207
J Biol Chem. 2005 Aug 26;280(34):30113-9
pubmed: 15983030
Am J Respir Crit Care Med. 2011 Mar 15;183(6):734-42
pubmed: 20889904
Am J Physiol Lung Cell Mol Physiol. 2016 Feb 1;310(3):L232-9
pubmed: 26608528
Am J Respir Crit Care Med. 2022 Jan 1;205(1):129-133
pubmed: 34748720
Dev Cell. 2020 Jun 8;53(5):514-529.e3
pubmed: 32425701
Am J Respir Crit Care Med. 2020 Sep 1;202(5):756-759
pubmed: 32663409
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Eur Respir J. 2018 Apr 26;51(4):
pubmed: 29545277
JAMA. 2020 May 26;323(20):2052-2059
pubmed: 32320003
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Am J Respir Crit Care Med. 2018 Nov 15;198(10):1254-1267
pubmed: 29750543
Inhal Toxicol. 2014 Jan;26(1):14-22
pubmed: 24417403
Front Med (Lausanne). 2021 Jan 18;7:627278
pubmed: 33537336
Am J Respir Crit Care Med. 2016 Feb 1;193(3):251-8
pubmed: 26414484
Mayo Clin Proc. 2018 Oct;93(10):1488-1502
pubmed: 30286833
Am J Respir Crit Care Med. 2017 Jun 1;195(11):1464-1476
pubmed: 28085500
Respir Med. 2020 Jun;167:105941
pubmed: 32421537
J Mol Neurosci. 2008 Jun;35(2):151-60
pubmed: 18369742
Nature. 2005 Jul 7;436(7047):112-6
pubmed: 16001071
Am J Respir Crit Care Med. 2020 Jun 15;201(12):1557-1559
pubmed: 32329629
Am J Physiol Regul Integr Comp Physiol. 2018 Nov 1;315(5):R895-R906
pubmed: 30088946
Elife. 2020 Apr 02;9:
pubmed: 32228860
Lancet Infect Dis. 2020 Sep;20(9):1034-1042
pubmed: 32422204
Mol Syst Biol. 2020 Jul;16(7):e9610
pubmed: 32715618
Eur Respir J. 2020 May 14;55(5):
pubmed: 32269089
Am J Respir Crit Care Med. 2019 Dec 1;200(11):1434-1439
pubmed: 31348682
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Allergy. 2020 Jul;75(7):1730-1741
pubmed: 32077115
Am J Respir Crit Care Med. 2020 Jul 1;202(1):8-10
pubmed: 32437628
Nature. 2020 Sep;585(7826):588-590
pubmed: 32698190
Nat Genet. 2021 Feb;53(2):205-214
pubmed: 33432184
Am J Respir Crit Care Med. 2020 Aug 1;202(3):471-472
pubmed: 32530714
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L84-96
pubmed: 19411314
Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):
pubmed: 33811184
Am J Med. 2018 Sep;131(9S):1-6
pubmed: 29778456
Nat Med. 2020 May;26(5):681-687
pubmed: 32327758
Nicotine Tob Res. 2020 Aug 24;22(9):1653-1656
pubmed: 32399563