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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 单核细胞/巨噬细胞和激活的淋巴细胞通过正常大脑的流量，并且在炎症状况（例如HIVE）（HIVE）等炎症状况中增加了这种运输。 Hive的特征是巨噬细胞的周血管积累。 在此过程中，最早的事件是在人类中很难理解，难以解决的。神经辅助的SIV感染的猕猴模型已证明单核细胞在疾病早期迁移到大脑中，与SIV峰值病毒血症一致。尚未描述启动单核细胞迁移到中枢神经系统的迁移的趋化信号。在这里，我们将星形胶质细胞描述为趋于基础单核细胞运输中枢神经系统的趋化因子的来源，而CCL7产量的增加可能是导致神经助剂的贩运增加的原因。我们以前已经发表了体内互补的体内工作，证明了SIV感染猕猴大脑中MCP-3/CCL7（和其他趋化因子）的存在。在这里，我们证明了MCP-3/CCL7是星形胶质细胞产生的重要趋化因子，CCL7负责基础单核细胞募集水平，并且TNF的CCL7产生迅速增加，因此很可能在SIV/HIV启动神经毒性中起着至关重要的作用。