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.

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