Analysis of human lung endothelial cells for susceptibility to HIV type 1 infection, coreceptor expression, and cytotoxicity of gp120 protein

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 c ells in the lung. However, other cell types in the lung could participate i n HIV-mediated lung pathology and their role has not been investigated, The aims of this study were to determine if human lung microvascular endotheli al cells (HLMEC) express HIV receptor and coreceptors, and if HIV can direc tly infect HLMEC. Specifically, we wished to determine if these cells const itute a viral reservoir in the lung, and if HIV-1 envelope proteins induce cytotoxic effects on HLMEC. Our results showed that by flow cytometry, HLME C 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 du al-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 apopto tic cell death of HLMEC, These data support the hypothesis that no producti ve HIV-1 infection of HLMEC occurs in vitro. This suggests that in who, HLM EC may not be a major reservoir of HIV in the lung and the primary route fo r HIV invasion of the lung. Thus, while other mechanisms must play a role i n HIV invasion and subsequent dissemination in the lung, lung endothelial c ells do represent potential targets for the lethal effects of HIV viral pro teins.