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SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis

BACKGROUND: Smokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19. METHODS: This cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers CO...

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Autores principales: Brake, Samuel James, Eapen, Mathew Suji, McAlinden, Kielan Darcy, Markos, James, Haug, Greg, Larby, Josie, Chia, Collin, Hardikar, Ashutosh, Singhera, Gurpreet Kaur, Hackett, Tillie L, Lu, Wenying, Sohal, Sukhwinder Singh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761078/
https://www.ncbi.nlm.nih.gov/pubmed/35046647
http://dx.doi.org/10.2147/COPD.S329783
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author Brake, Samuel James
Eapen, Mathew Suji
McAlinden, Kielan Darcy
Markos, James
Haug, Greg
Larby, Josie
Chia, Collin
Hardikar, Ashutosh
Singhera, Gurpreet Kaur
Hackett, Tillie L
Lu, Wenying
Sohal, Sukhwinder Singh
author_facet Brake, Samuel James
Eapen, Mathew Suji
McAlinden, Kielan Darcy
Markos, James
Haug, Greg
Larby, Josie
Chia, Collin
Hardikar, Ashutosh
Singhera, Gurpreet Kaur
Hackett, Tillie L
Lu, Wenying
Sohal, Sukhwinder Singh
author_sort Brake, Samuel James
collection PubMed
description BACKGROUND: Smokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19. METHODS: This cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 were never-smoking normal controls (NC). Immunostaining for ACE2, Furin, and TMPRSS2 was performed and analysed for percent expression in small airway epithelium (SAE) and counts for positively and negatively stained type 2 pneumocytes and alveolar macrophages (AMs) were done using Image ProPlus V7.0. Furthermore, primary small airway epithelial cells (pSAEC) were analysed by immunofluorescence after exposure to cigarette smoke extract (CSE). RESULTS: ACE2, Furin, and TMPRSS2 expression significantly increased in SAE and type 2 pneumocytes in all the subjects (except Furin for NLFS) compared to NC (p < 0.001). Similar significance was observed for ACE2 positive AM (p < 0.002), except COPD-ES, which decreased in ACE2 positive AMs (p < 0.003). Total type 2 pneumocytes and AMs significantly increased in the pathological groups compared to NC (p < 0.01), except SAD (p = 0.08). However, AMs are significantly reduced in COPD-ES (p < 0.003). Significant changes were observed for tissue co-expression of Furin and TMPRSS2 with ACE2 in SAE, type 2 pneumocytes and AMs. These markers also negatively correlated with lung function parameters, such as FEV(1)/FVC % predicted, FEF25-75%, DLCO% predicted. A strong co-localisation and expression for ACE2 (p < 0.0001), Furin (p < 0.01), and TMPRSS2 (p < 0.0001) was observed in pSAEC treated with 1% CSE than controls. DISCUSSION: The increased expression of ACE2, TMPRSS2 and Furin, in the SAE, type 2 pneumocytes and AMs of smokers and COPD are detrimental to lung function and proves that these patient groups could be more susceptible to severe COVID-19 infection. Increased type 2 pneumocytes suggest that these patients are vulnerable to developing post-COVID-19 interstitial pulmonary fibrosis or fibrosis in general. There could be a silently developing interstitial pathology in smokers and patients with COPD. This is the first comprehensive study to report such changes.
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spelling pubmed-87610782022-01-18 SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis Brake, Samuel James Eapen, Mathew Suji McAlinden, Kielan Darcy Markos, James Haug, Greg Larby, Josie Chia, Collin Hardikar, Ashutosh Singhera, Gurpreet Kaur Hackett, Tillie L Lu, Wenying Sohal, Sukhwinder Singh Int J Chron Obstruct Pulmon Dis Original Research BACKGROUND: Smokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19. METHODS: This cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 were never-smoking normal controls (NC). Immunostaining for ACE2, Furin, and TMPRSS2 was performed and analysed for percent expression in small airway epithelium (SAE) and counts for positively and negatively stained type 2 pneumocytes and alveolar macrophages (AMs) were done using Image ProPlus V7.0. Furthermore, primary small airway epithelial cells (pSAEC) were analysed by immunofluorescence after exposure to cigarette smoke extract (CSE). RESULTS: ACE2, Furin, and TMPRSS2 expression significantly increased in SAE and type 2 pneumocytes in all the subjects (except Furin for NLFS) compared to NC (p < 0.001). Similar significance was observed for ACE2 positive AM (p < 0.002), except COPD-ES, which decreased in ACE2 positive AMs (p < 0.003). Total type 2 pneumocytes and AMs significantly increased in the pathological groups compared to NC (p < 0.01), except SAD (p = 0.08). However, AMs are significantly reduced in COPD-ES (p < 0.003). Significant changes were observed for tissue co-expression of Furin and TMPRSS2 with ACE2 in SAE, type 2 pneumocytes and AMs. These markers also negatively correlated with lung function parameters, such as FEV(1)/FVC % predicted, FEF25-75%, DLCO% predicted. A strong co-localisation and expression for ACE2 (p < 0.0001), Furin (p < 0.01), and TMPRSS2 (p < 0.0001) was observed in pSAEC treated with 1% CSE than controls. DISCUSSION: The increased expression of ACE2, TMPRSS2 and Furin, in the SAE, type 2 pneumocytes and AMs of smokers and COPD are detrimental to lung function and proves that these patient groups could be more susceptible to severe COVID-19 infection. Increased type 2 pneumocytes suggest that these patients are vulnerable to developing post-COVID-19 interstitial pulmonary fibrosis or fibrosis in general. There could be a silently developing interstitial pathology in smokers and patients with COPD. This is the first comprehensive study to report such changes. Dove 2022-01-11 /pmc/articles/PMC8761078/ /pubmed/35046647 http://dx.doi.org/10.2147/COPD.S329783 Text en © 2022 Brake et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Brake, Samuel James
Eapen, Mathew Suji
McAlinden, Kielan Darcy
Markos, James
Haug, Greg
Larby, Josie
Chia, Collin
Hardikar, Ashutosh
Singhera, Gurpreet Kaur
Hackett, Tillie L
Lu, Wenying
Sohal, Sukhwinder Singh
SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title_full SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title_fullStr SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title_full_unstemmed SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title_short SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis
title_sort sars-cov-2 (covid-19) adhesion site protein upregulation in small airways, type 2 pneumocytes, and alveolar macrophages of smokers and copd – possible implications for interstitial fibrosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761078/
https://www.ncbi.nlm.nih.gov/pubmed/35046647
http://dx.doi.org/10.2147/COPD.S329783
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