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Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections


Eapen, MS and Lu, W and Hackett, TL and Singhera, GR and Thompson, IE and McAlinden, KD and Hardikar, A and Weber, HC and Haug, G and Wark, PAB and Chia, C and Sohal, SS, Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections, American Journal of Physiology, 320, (1) pp. L158-L163. ISSN 1040-0605 (2021) [Refereed Article]

Copyright Statement

Copyright 2021 the American Physiological Society

DOI: doi:10.1152/ajplung.00437.2020


Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack. The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with COPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were neversmoking normal controls. Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using Image ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.

Item Details

Item Type:Refereed Article
Keywords:COPD, SARS-CoV-2, ACE2, COVID-19, smoking
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Eapen, MS (Dr Mathew Eapen)
UTAS Author:Lu, W (Dr Monica Lu)
UTAS Author:Thompson, IE (Miss Isobel Thompson)
UTAS Author:McAlinden, KD (Mr Kielan McAlinden)
UTAS Author:Hardikar, A (Dr Ashutosh Hardikar)
UTAS Author:Weber, HC (Associate Professor Heinrich Weber)
UTAS Author:Haug, G (Dr Greg Haug)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:142689
Year Published:2021
Web of Science® Times Cited:13
Deposited By:Health Sciences
Deposited On:2021-02-05
Last Modified:2021-06-30

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