PRODUCTION OF CCL7 BY ASTROCYTES: SIV NEUROINVASION AND AIDS ENCEPHALITIS

星形胶质细胞产生 CCL7：SIV 神经侵袭和艾滋病脑炎

• 批准号: 7958688
• 负责人: ANDREW G MACLEAN
• 金额: $ 6.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958688
• 关键词: AIDS neuropathy; Acquired Immunodeficiency Syndrome; Activated Lymphocyte; Address; Astrocytes; Autologous; Blood - brain barrier anatomy; Brain; CCL7 gene; Cells; Computer Retrieval of Information on Scientific Projects Database; Disease; Encephalitis; Endothelial Cells; Event; Funding; Grant; HIV encephalitis; Human; Immigration; Inflammatory; Institution; Leukocytes; Macaca; Modeling; Mononuclear; Play; Primates; Process; Production; Publishing; Research; Research Personnel; Resources; Role; SIV; Signal Transduction; Source; United States National Institutes of Health; Viremia; Work; chemokine; in vitro Model; in vivo; macrophage; monocyte; trafficking

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 单核细胞/巨噬细胞和活化的淋巴细胞通过正常大脑运输，并且这种运输在艾滋病毒脑炎 (HIVE) 等炎症性疾病中会增加。 HIVE的部分特征是血管周围巨噬细胞的积聚。 对于这一过程中最早的事件我们知之甚少，并且很难或不可能在人类中解决。 从 SIV 感染的神经艾滋病猕猴模型中可以看出，在疾病早期，单核细胞迁移到大脑中，与 SIV 病毒血症峰值一致。尚未描述促进第一个单核细胞穿过血脑屏障的趋化信号。在这里，我们描述了使用涉及自体星形胶质细胞和微血管脑内皮细胞的猕猴血脑屏障体外模型来检查白细胞招募到中枢神经系统的早期事件。我们之前发表了补充性体内研究，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 MCP-3/CCL7 是星形胶质细胞产生的重要趋化因子，并且它可能在单核细胞/巨噬细胞向 CNS 的基础水平运输以及 SIV/HIV 进入大脑的过程中发挥重要作用。