- Title
- 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
- Creator
- Eapen, Mathew Suji; Lu, Wenying; Chia, Collin; Sohal, Sukhwinder Singh; Hackett, Tillie L.; Singhera, Gurpreet Kaur; Thompson, Isobel E.; McAlinden, Kielan Darcy; Hardikar, Ashutosh; Weber, Heinrich C.; Haug, Greg; Wark, Peter A. B.
- Relation
- American Journal of Physiology - Lung Cellular and Molecular Physiology Vol. 320, Issue 1, p. L158-L163
- Publisher Link
- http://dx.doi.org/10.1152/AJPLUNG.00437.2020
- Publisher
- American Physiological Society
- Resource Type
- journal article
- Date
- 2021
- Description
- 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 never-smoking 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.
- Subject
- ACE2; COVID-19; COPD; electronic cigarettes; SARS-CoV-2; smoking
- Identifier
- http://hdl.handle.net/1959.13/1425754
- Identifier
- uon:38305
- Identifier
- ISSN:1040-0605
- Language
- eng
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