PRODUCTION OF CCL7 BY ASTROCYTES: SIV NEUROINVASION AND AIDS ENCEPHALITIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 单核/巨噬细胞和激活的淋巴细胞通过正常大脑进行运输，这种运输在炎症性条件下增加，如艾滋病毒脑炎(HIVE)。蜂窝的部分特征是巨噬细胞在血管周围堆积。这一过程中最早的事件很少被理解，很难或不可能在人类身上解决。从SIV感染的神经艾滋病猕猴模型来看，似乎在疾病早期单核细胞迁移到大脑中，这与SIV病毒血症的高峰期一致。促进第一批单核细胞穿越血脑屏障的趋化信号尚未被描述。在这里，我们描述了一个猕猴血脑屏障的体外模型，包括自体星形胶质细胞和微血管脑内皮细胞，以检查白细胞募集到中枢神经系统的非常早期的事件。我们之前已经发表了补充的体内工作，证明了SIV感染的猕猴大脑中存在MCP-3/CCL7(和其他趋化因子)。在这里，我们证明了MCP-3/CCL7是星形胶质细胞产生的一种重要的趋化因子，它可能在单细胞/巨噬细胞运输到中枢神经系统的基础水平上发挥重要作用，从而使SIV/HIV进入大脑。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Monocyte/macrophages and activated lymphocytes traffic through normal brain, and this trafficking is increased in inflammatory conditions such as HIV encephalitis (HIVE). HIVE is characterized in part by perivascular accumulations of macrophages. The earliest events in this process are poorly understood and difficult or impossible to address in humans. From the SIV-infected macaque model of neuroAIDS it appears there is an immigration of monocytes into the brain early in disease, coincident with peak SIV viremia. The chemotactic signals that facilitate the first mononuclear cells to traverse the blood-brain barrier have not been described. Here we describe the use of an in vitro model of the macaque blood-brain barrier involving autologous astrocytes and microvascular brain endothelial cells to examine very early events in leukocyte recruitment to the CNS. We have previously published complementary in vivo work demonstrating the presence of MCP-3/CCL7 (and other chemokines) within the brain of SIV-infected macaques. Here we demonstrate that MCP-3/CCL7 is a significant chemokine produced by astrocytes and that it is likely to play a major role in the basal level of monoycte/macrophage trafficking to the CNS and thus entry of SIV/HIV into the brain.