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
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
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DOI：
10.1152/ajplung.00437.2020
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发表时间：
2021-01-01
影响因子：
4.9
通讯作者：
Sohal, Sukhwinder Singh
中科院分区：
文献类型：
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作者：
Eapen, Mathew Suji;Lu, Wenying;Sohal, Sukhwinder Singh
吸烟者和慢性阻塞性肺疾病（COPD）的肺部严重受损，易受严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的攻击。增强的SARS-CoV-2附着受体蛋白ACE 2沿着内吞空泡增加的危险组合将使病毒附着、进入和复制成为可能。本研究的目的是确定吸烟者和COPD患者气道中是否存在SARS-CoV-2宿主附着受体血管紧张素转换酶-2（ACE 2）沿着内吞空泡、早期内体抗原-1（EEA 1）、晚期内体标记物RAB 7、组织蛋白酶-L和溶酶体相关膜蛋白-1（LAMP-1）作为溶酶体标记物。研究设计为横断面，共涉及39例患者的肺切除术，其中包括19例慢性阻塞性肺疾病全球倡议（GOLD）I期或GOLD II期COPD患者，其中9例为COPD当前吸烟者（COPD-CS），10例为COPD既往吸烟者（COPD-ES），10例为肺功能正常的吸烟者，10例为从不吸烟的正常对照。对ACE 2、EEA 1、RAB 7和组织蛋白酶-L进行免疫染色。提供了患者组ACE 2、EEA 1、RAB 7和组织蛋白酶-L表达模式的比较描述。此外，使用Image ProPlus v7.0软件，将LAMP-1溶胞素的染色强度测量为LAMP-1染色面积/上皮或上皮下总面积的比率。LAMP-1表达与吸烟史呈正相关，而在COPD中，LAMP-1与肺功能呈负相关。吸烟者和COPD患者的小气道中ACE 2蛋白沿着内吞空泡（如早期/晚期内体和溶酶体）的活跃存在提供了证据，表明这些患者群体可能更容易感染COVID-19。
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 lysosonnes 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 lysosonnes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.