Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Laryngoscope. 2021 Mar;131(3):E932-E939. doi: 10.1002/lary.29132. Epub 2020 Oct 19.
Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS-CoV-2.
To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.
Co-expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.
A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19.
NA Laryngoscope, 131:E932-E939, 2021.
由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）患者不仅表现出呼吸系统症状，还表现出化学敏感障碍症状。SARS-CoV-2 的细胞进入依赖于其刺突蛋白与细胞受体血管紧张素转换酶 2（ACE2）的结合，以及随后由宿主细胞蛋白酶（包括跨膜丝氨酸蛋白酶 2（TMPRSS2））进行的刺突蛋白引发。因此，ACE2 和 TMPRSS2 的高表达被认为增强了 SARS-CoV-2 的入侵能力。
为了阐明 SARS-CoV-2 引起的呼吸道疾病的潜在组织学机制，我们使用免疫组织化学法研究了 ACE2 和 TMPRSS2 蛋白在大鼠的舌、硬腭带部分鼻组织、喉带下咽、气管、食管和肺的呼吸道中的表达。
ACE2 和 TMPRSS2 蛋白在舌的味蕾、鼻上皮、气管、细支气管和肺泡中均有不同程度的共表达。值得注意的是，外周肺泡中的 TMPRSS2 表达比中央肺泡更为明显。这些结果与 COVID-19 的报道临床症状一致，如味觉丧失、嗅觉丧失和呼吸功能障碍。
根据 ACE2 和 TMPRSS2 的表达水平，推测广泛的器官可能受到 SARS-CoV-2 的影响。肺中 TMPRSS2 的差异分布表明，TMPRSS2 表达可能使 COVID-19 症状恶化。本研究可能为进一步研究 COVID-19 的发病机制提供潜在线索。
无 喉镜，131：E932-E939，2021。
