Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients:: relation to the acute lung injury and pathogenesis of SARS
Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients:: relation to the acute lung injury and pathogenesis of SARS
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DOI：
10.1002/path.2067
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发表时间：
2006-11-01
影响因子：
7.3
通讯作者：
Jiang, S.
中科院分区：
文献类型：
--
作者：
He, L.;Ding, Y.;Jiang, S.
作者先前已经证明，急性肺损伤(ALI)会在死于严重急性呼吸综合征(SARS)的患者中产生广泛的病理过程，并且在这些患者的肺部和其他器官和组织中可以检测到SARS冠状病毒(SARS-CoV)核蛋白。本研究采用免疫组织化学和原位杂交的方法，对4例SARS患者尸检组织中血管紧张素转换酶2、S蛋白和一些促炎细胞因子的表达进行了分析。SARS-CoV S蛋白及其核糖核酸仅在肺等器官的ACE2(+)细胞中检测到，提示ACE2表达的细胞是SARS-CoV体内感染的主要靶点。感染SARS冠状病毒的ACE2(+)细胞高水平表达PIC，而未感染的ACE2(+)细胞不表达PIC。这些结果表明，感染SARS-CoV的细胞会产生高水平的PIC，这可能会对肺和其他器官造成免疫介导的损害，导致ALI，并随后导致多器官功能障碍。因此，应用PIC拮抗剂可能会降低SARS的严重程度和死亡率。版权所有(C)2006年大不列颠和爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
The authors have previously shown that acute lung injury (ALI) produces a wide spectrum of pathological processes in patients who die of severe acute respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV) nucleoprotein is detectable in the lungs, and other organs and tissues, in these patients. In the present study, immunohistochemistry (IHC) and in situ hybridization (ISH) assays were used to analyse the expression of angiotensin-converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory cytokines (PICs) including MCP-1, TGF-beta 1, TNF-alpha, IL-1 beta, and IL-6 in autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its RNA were only detected in ACE2(+) cells in the lungs and other organs, indicating that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2(+) cells, but not in the uninfected cells. These results suggest that cells infected by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated damage to the lungs and other organs, resulting in ALI and, subsequently, multi-organ dysfunction. Therefore application of PIC antagonists may reduce the severity and mortality of SARS. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.