{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:22:20Z","timestamp":1770492140904,"version":"3.49.0"},"reference-count":27,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100001061","name":"Clifford Craig Foundation Launceston General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001061","name":"Rebecca L. Cooper Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001061","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p> 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. <\/jats:p>","DOI":"10.1152\/ajplung.00437.2020","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T12:21:16Z","timestamp":1605097276000},"page":"L158-L163","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":21,"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"],"prefix":"10.1152","volume":"320","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0570-7059","authenticated-orcid":false,"given":"Mathew Suji","family":"Eapen","sequence":"first","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-2276","authenticated-orcid":false,"given":"Wenying","family":"Lu","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tillie L.","family":"Hackett","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurpreet Kaur","family":"Singhera","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isobel E.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kielan Darcy","family":"McAlinden","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashutosh","family":"Hardikar","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"},{"name":"Department of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinrich C.","family":"Weber","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"},{"name":"Department of Respiratory Medicine, Tasmanian Health Services, North West Hospital, Burnie, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Haug","sequence":"additional","affiliation":[{"name":"Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia"},{"name":"Department of Respiratory Medicine, Launceston General Hospital, Launceston, Tasmania, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-6126","authenticated-orcid":false,"given":"Peter A. 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