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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
Citation
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
Abstract
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 |
| Downloads: | 0 |
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