PRODUCTION OF CCL7 BY ASTROCYTES: SIV NEUROINVASION AND AIDS ENCEPHALITIS

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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.