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: 8358099
• 负责人: ANDREW G MACLEAN
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358099
• 关键词: AIDS neuropathy; Acquired Immunodeficiency Syndrome; Activated Lymphocyte; Address; Astrocytes; Brain; CCL7 gene; Cells; Disease; Emigrations; Encephalitis; Event; Funding; Grant; HIV; HIV encephalitis; Human; Inflammatory; Macaca; Modeling; Mononuclear; National Center for Research Resources; Play; Primates; Principal Investigator; Process; Production; Publishing; Research; Research Infrastructure; Resources; Role; SIV; Signal Transduction; Source; TNF gene; United States National Institutes of Health; Viremia; Work; chemokine; cost; in vivo; macrophage; migration; monocyte; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. The SIV-infected macaque model of neuroAIDS has demonstrated migration of monocytes into the brain early in disease, coincident with peak SIV viremia. The chemotactic signals that initiate the increased emigration of mononuclear cells into the CNS have not been described. Here we describe astrocytes as a source of chemokines to facilitate basal levels of monocyte trafficking to CNS and that increased CCL7 production is probably responsible for initiating the increased trafficking in neuroAIDS. 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, that CCL7 is responsible for basal levels of monocyte recruitment and that production of CCL7 is rapidly increased by TNF and thus likely plays a critical role in initiating neuroinvasion by SIV/HIV.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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。感染 SIV 的神经艾滋病猕猴模型已证明单核细胞在疾病早期迁移到大脑中，与 SIV 病毒血症峰值一致。尚未描述引发单核细胞向中枢神经系统迁移增加的趋化信号。在这里，我们将星形胶质细胞描述为趋化因子的来源，以促进单核细胞向中枢神经系统运输的基础水平，并且 CCL7 产量的增加可能是导致神经艾滋病运输增加的原因。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，CCL7 负责单核细胞募集的基础水平，并且 CCL7 的产生通过 TNF 迅速增加，因此可能在 SIV/HIV 引发的神经侵袭中发挥关键作用。