Analysis of human lung endothelial cells for susceptibility to HIV type 1 infection, coreceptor expression, and cytotoxicity of gp120 protein
Analysis of human lung endothelial cells for susceptibility to HIV type 1 infection, coreceptor expression, and cytotoxicity of gp120 protein
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DOI：
10.1089/088922201750056771
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发表时间：
2001-01-01
影响因子：
1.5
通讯作者：
Grammas, P
中科院分区：
文献类型：
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作者：
Kanmogne, GD;Kennedy, RC;Grammas, P
肺部是HIV感染的潜在靶点，许多患者的AIDS发作与严重的肺部并发症有关。T淋巴细胞和肺泡巨噬细胞形成肺中的大多数HIV感染细胞。然而，肺中的其他细胞类型也可以参与HIV介导的肺病理学，并且它们的作用尚未被研究。本研究的目的是确定人肺微血管内皮细胞（HLMEC）是否表达HIV受体和辅助受体，以及HIV是否可以直接感染HLMEC。具体而言，我们希望确定这些细胞是否构成肺中的病毒储库，以及HIV-1包膜蛋白是否诱导对HLMEC的细胞毒性作用。流式细胞仪检测结果显示HLMEC表面不表达CXCR 4和CCR 5。RT-PCR检测HLMEC中CXCR 4和CCR 5 mRNA的表达，而CD 4 mRNA的表达不明显。经p24抗原捕获ELISA、逆转录酶试验、RT-PCR和DNA PCR检测，两株双嗜性HIV-1分离株均未感染HLMEC。然而，重组HIV-1 gp 120制剂诱导HLMEC凋亡细胞死亡，这些数据支持体外HLMEC不发生生产性HIV-1感染的假设。这表明，在世卫组织中，HLMEC可能不是肺中HIV的主要储存库，也不是HIV侵入肺的主要途径。因此，虽然其他机制必须在HIV侵入和随后在肺中的传播中发挥作用，但肺内皮细胞确实是HIV病毒蛋白致死作用的潜在靶点。
The lung represents a potential target during HIV infection, and the onset of AIDS is associated with severe pulmonary complications in many patients. T-lymphocytes and alveolar macrophages form the majority of HIV-infected cells in the lung. However, other cell types in the lung could participate in HIV-mediated lung pathology and their role has not been investigated, The aims of this study were to determine if human lung microvascular endothelial cells (HLMEC) express HIV receptor and coreceptors, and if HIV can directly infect HLMEC. Specifically, we wished to determine if these cells constitute a viral reservoir in the lung, and if HIV-1 envelope proteins induce cytotoxic effects on HLMEC. Our results showed that by flow cytometry, HLMEC failed to express any CXCR4 or CCR5 on their surface. In contrast, RT-PCR revealed the presence of CXCR4 and CCR5 mRNA, hut not CD4 in HLMEC. Two dual-tropic HIV-1 isolates failed to infect HLMEC in vitro, as determined by (1) p24 antigen capture ELISA, (2) reverse transcriptase assay, RT-PCR, and (3) DNA PCR. However, a recombinant HIV-1 gp120 preparation induced apoptotic cell death of HLMEC, These data support the hypothesis that no productive HIV-1 infection of HLMEC occurs in vitro. This suggests that in who, HLMEC may not be a major reservoir of HIV in the lung and the primary route for HIV invasion of the lung. Thus, while other mechanisms must play a role in HIV invasion and subsequent dissemination in the lung, lung endothelial cells do represent potential targets for the lethal effects of HIV viral proteins.