Conant K, Garzino-Demo A, Nath A, McArthur J C, Halliday W, Power C, Gallo R C, Major E O
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Building 36, Room 5W21, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3117-21. doi: 10.1073/pnas.95.6.3117.
Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.
活化的单核细胞会释放多种物质，包括炎性细胞因子和类二十烷酸，这些物质对中枢神经系统细胞具有高度毒性。由于中枢神经系统的单核细胞浸润与HIV-1相关痴呆密切相关，因此有人提出单核细胞衍生的毒素介导神经系统损伤。在本研究中，我们发现HIV-1反式激活蛋白Tat显著增加星形胶质细胞单核细胞趋化蛋白-1（MCP-1）的表达和释放。未观察到β-趋化因子（对单核细胞选择性相对较低，包括RANTES、巨噬细胞炎性蛋白-1α和巨噬细胞炎性蛋白-1β）从星形胶质细胞释放。我们还发现MCP-1在HIV-1相关痴呆患者的大脑中表达，并且在患有这种疾病的患者的脑脊液中，在所检测的β-趋化因子中，仅能检测到MCP-1。这些数据共同表明大脑中HIV-1的存在与单核细胞浸润之间存在潜在联系，而单核细胞浸润可能在很大程度上导致痴呆。
