人类鼻腔和嗅球中 SARS-CoV-2 进入蛋白 ACE2 的证据。
Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb.
机构信息
Institute of Neuroanatomy and Developmental Biology, Eberhard Karls University Tübingen, Tübingen, Germany.
Institute of Neuroanatomy and Developmental Biology, Eberhard Karls University Tübingen, Tübingen, Germany,
出版信息
Cells Tissues Organs. 2020;209(4-6):155-164. doi: 10.1159/000513040. Epub 2021 Jan 22.
Usually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough, but frequently also with anosmia and neurological symptoms. Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to the central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium as well as in the respiratory epithelium of the nasal septum, the nasal conchae, and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium as well as in the basal cells, glandular cells, and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly, ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia via the olfactory pathway.
通常,由 SARS-CoV2 引起的大流行 COVID-19 疾病表现为轻度呼吸道症状,如发热、咳嗽,但经常也伴有嗅觉丧失和神经系统症状。病毒与细胞的融合由血管紧张素转换酶 2(ACE2)和跨膜丝氨酸蛋白酶 2(TMPRSS2)介导,其器官表达模式决定了病毒的嗜性。临床症状表明,病毒迅速传播到中枢神经系统,导致包括病毒性脑膜炎在内的严重症状。在这里,我们提供了 ACE2 和 TMPRSS2 蛋白在人类死后鼻和嗅组织中的全面表达图谱。通过对相应细胞类型进行免疫标记,补充了人类鼻子的矢状切片,代表了不同解剖定义的区域,包括嗅上皮、鼻甲的呼吸上皮和副鼻窦,以及难以接近的人类嗅球。ACE2 可在嗅上皮以及鼻中隔、鼻甲和副鼻窦的呼吸上皮中检测到。ACE2 位于嗅上皮中的支持细胞和腺细胞以及呼吸上皮中的基底细胞、腺细胞和上皮细胞中。有趣的是,ACE2 不在成熟或未成熟的嗅觉受体神经元和嗅上皮中的基底细胞中表达。同样,ACE2 也不在嗅球阳性的嗅球神经元中定位。相反,TMPRSS2 也可在嗅上皮中的支持细胞和腺细胞中检测到。我们的研究结果为 ACE2 和 TMPRSS2 在人鼻、嗅上皮和嗅球中的表达提供了基本的解剖学证据。因此,它们对于旨在通过嗅觉途径阐明 SARS-CoV2 引起的嗅觉丧失症状的未来研究具有重要意义。
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