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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 单核细胞/巨噬细胞和活化的淋巴细胞通过正常大脑运输，并且这种运输在炎症性疾病如HIV脑炎（HIVE）中增加。HIVE的部分特征在于巨噬细胞的血管周围积聚。 人们对这一过程中最早的事件知之甚少，并且很难或不可能在人类身上解决。SIV感染的神经AIDS猕猴模型已经证明单核细胞在疾病早期迁移到脑中，与SIV病毒血症高峰一致。启动单核细胞向CNS迁移增加的趋化信号尚未描述。在这里，我们描述星形胶质细胞作为趋化因子的来源，以促进基础水平的单核细胞运输到中枢神经系统，增加CCL 7的生产可能是负责启动增加贩运neuroAIDS。我们先前已经发表了补充的体内工作，证明了MCP-3/CCL 7（和其他趋化因子）在SIV感染的猕猴脑内的存在。在这里，我们证明了MCP-3/CCL 7是一种重要的趋化因子产生的星形胶质细胞，CCL 7是负责基础水平的单核细胞募集和生产的CCL 7是迅速增加的TNF，因此可能起着关键作用，在启动神经入侵SIV/HIV。