Cargando…

Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2

Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Masso-Silva, Jorge A., Moshensky, Alexander, Shin, John, Olay, Jarod, Nilaad, Sedtavut, Advani, Ira, Bojanowski, Christine M., Crotty, Shane, Li, Wei Tse, Ongkeko, Weg M., Singla, Sunit, Crotty Alexander, Laura E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194307/
https://www.ncbi.nlm.nih.gov/pubmed/34122126
http://dx.doi.org/10.3389/fphys.2021.649604
_version_ 1783706393204752384
author Masso-Silva, Jorge A.
Moshensky, Alexander
Shin, John
Olay, Jarod
Nilaad, Sedtavut
Advani, Ira
Bojanowski, Christine M.
Crotty, Shane
Li, Wei Tse
Ongkeko, Weg M.
Singla, Sunit
Crotty Alexander, Laura E.
author_facet Masso-Silva, Jorge A.
Moshensky, Alexander
Shin, John
Olay, Jarod
Nilaad, Sedtavut
Advani, Ira
Bojanowski, Christine M.
Crotty, Shane
Li, Wei Tse
Ongkeko, Weg M.
Singla, Sunit
Crotty Alexander, Laura E.
author_sort Masso-Silva, Jorge A.
collection PubMed
description Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1–6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens via reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses via decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs.
format Online
Article
Text
id pubmed-8194307
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81943072021-06-12 Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2 Masso-Silva, Jorge A. Moshensky, Alexander Shin, John Olay, Jarod Nilaad, Sedtavut Advani, Ira Bojanowski, Christine M. Crotty, Shane Li, Wei Tse Ongkeko, Weg M. Singla, Sunit Crotty Alexander, Laura E. Front Physiol Physiology Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1–6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens via reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses via decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs. Frontiers Media S.A. 2021-05-31 /pmc/articles/PMC8194307/ /pubmed/34122126 http://dx.doi.org/10.3389/fphys.2021.649604 Text en Copyright © 2021 Masso-Silva, Moshensky, Shin, Olay, Nilaad, Advani, Bojanowski, Crotty, Li, Ongkeko, Singla and Crotty Alexander. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Masso-Silva, Jorge A.
Moshensky, Alexander
Shin, John
Olay, Jarod
Nilaad, Sedtavut
Advani, Ira
Bojanowski, Christine M.
Crotty, Shane
Li, Wei Tse
Ongkeko, Weg M.
Singla, Sunit
Crotty Alexander, Laura E.
Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title_full Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title_fullStr Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title_full_unstemmed Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title_short Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
title_sort chronic e-cigarette aerosol inhalation alters the immune state of the lungs and increases ace2 expression, raising concern for altered response and susceptibility to sars-cov-2
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194307/
https://www.ncbi.nlm.nih.gov/pubmed/34122126
http://dx.doi.org/10.3389/fphys.2021.649604
work_keys_str_mv AT massosilvajorgea chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT moshenskyalexander chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT shinjohn chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT olayjarod chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT nilaadsedtavut chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT advaniira chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT bojanowskichristinem chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT crottyshane chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT liweitse chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT ongkekowegm chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT singlasunit chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2
AT crottyalexanderlaurae chronicecigaretteaerosolinhalationalterstheimmunestateofthelungsandincreasesace2expressionraisingconcernforalteredresponseandsusceptibilitytosarscov2