Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis
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DOI:
10.1002/path.1570
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发表时间:
2004-06-01
影响因子:
7.3
通讯作者:
van Goor, H
van Goor, H
中科院分区:
医学1区
文献类型:
--
作者:
Hamming, I;Timens, W;van Goor, H

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严重急性呼吸系统综合征(SARS)是一种主要通过呼吸道传播的急性传染病。一种独特的冠状病毒(SARS-CoV)已被确定为SARS的病原体。最近,一种名为血管紧张素转换酶2(ACE 2)的金属肽酶被鉴定为SARS冠状病毒的功能性受体。虽然ACE 2 mRNA已知存在于几乎所有器官中,但其蛋白表达在很大程度上是未知的。由于确定可能的感染途径对于理解SARS的发病机制和未来的治疗策略具有重要意义,因此本研究调查了ACE 2蛋白在各种人体器官(口腔和鼻粘膜、鼻咽、肺、胃、小肠、结肠、皮肤、淋巴结、胸腺、骨髓、脾、肝、肾和脑)中的定位。最显著的发现是ACE 2蛋白在肺泡上皮细胞和小肠肠上皮细胞的表面表达。此外,ACE 2存在于动脉和静脉内皮细胞和动脉平滑肌细胞在所有器官的研究。总之,ACE 2在人类肺和小肠的上皮细胞中大量存在,这可能为SARS-CoV提供了可能的进入途径。这种上皮表达,以及血管内皮中ACE 2的存在,也为理解SARS主要疾病表现的发病机制提供了第一步。版权所有(C)2004大不列颠和爱尔兰病理学会。出版社:John Wiley Sons,Ltd
Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.