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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
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 4.9 ) Pub Date : 2020-11-11 , DOI: 10.1152/ajplung.00437.2020
Mathew Suji Eapen 1 , Wenying Lu 1 , Tillie L. Hackett 2 , Gurpreet Kaur Singhera 3 , Isobel E. Thompson 1 , Kielan Darcy McAlinden 1 , Ashutosh Hardikar 1, 4 , Heinrich C. Weber 1, 5 , Greg Haug 1, 6 , Peter A. B. Wark 7, 8 , Collin Chia 1, 6 , Sukhwinder Singh Sohal 1
Affiliation  

Lungs of smokers and COPD are severely compromised and are susceptible to SARS-CoV-2 attack. The lethal 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 lysosome-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 GOLD stage I or stage II COPD, of which 9 were current smokers with COPD (COPD-CS), and 10 ex-smokers with COPD (COPD-ES), 10 normal lung function smokers (NLFS) and 10 were never smoking normal controls (NC). 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. Further, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1 stained areas per total area of epithelium or sub-epithelium, using Image ProPlus 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.

中文翻译:

吸烟者和COPD患者的小气道内吞机器和ACE2的失调可增加其对SARS-CoV-2(COVID-19)感染的敏感性

吸烟者和COPD的肺部受到严重危害,很容易受到SARS-CoV-2的攻击。增强的SARS-CoV-2附着受体蛋白ACE2的致死性结合以及胞吞液泡的增加将使病毒附着,进入和复制成为可能。该研究的目的是鉴定SARS-CoV-2宿主附着受体血管紧张素转化酶2(ACE2)以及内吞液泡,早期内体抗原1(EEA1),晚期内体标记RAB7,组织蛋白酶L的存在。吸烟者和COPD患者的呼吸道中的溶酶体标记物和溶酶体相关膜蛋白1(LAMP-1)。研究设计是横断面的,共涉及39例患者的肺部切除术,其中包括19例GOLD I期或II期COPD患者,其中9例目前吸烟的COPD(COPD-CS),10名COPD前吸烟者(COPD-ES),10名正常肺功能吸烟者(NLFS)和10名从未吸烟的正常对照(NC)。对ACE2,EEA1,RAB7和组织蛋白酶-L进行了免疫染色。为患者组提供了ACE2,EEA1,RAB7和组织蛋白酶L表达模式的比较说明。此外,使用Image ProPlus软件,将LAMP-1溶酶体的染色强度测量为LAMP-1染色面积/上皮或上皮下总面积的比率。LAMP-1表达与患者吸烟史呈正相关,而在COPD中LAMP-1与肺功能呈负相关。
更新日期:2020-11-12
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