title: HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes.
abstract: AIDS dementia is characterized by neuronal loss in association with synaptic damage. A central predictor for clinical onset of these symptoms is the infiltration of monocytes and macrophages into CNS parenchyma. Chronic HIV-1 infection of monocytes also allows these cells to serve as reservoirs for persistent viral infection. Using a coculture of endothelial cells and astrocytes that models several aspects of the human blood-brain barrier, we examined the mechanism whereby the HIV-derived factor Tat may facilitate monocyte transmigration. We demonstrate that treatment of cocultures on the astrocyte side with HIV-1 Tat induced significant monocyte chemoattractant protein (MCP)-1 protein. Astrocytes, but not endothelial cells, were the source of this MCP-1 expression. Supernatants from Tat-treated cocultures induced significant monocyte transmigration, which was detected by 2.5 h after the addition of PBMC. Pretreatment of the supernatants from Tat-stimulated cocultures with an Ab to MCP-1 completely blocked monocyte transmigration. Flow cytometric analysis of Tat-stimulated PBMC demonstrated that Tat up-regulated expression of the chemokine receptor, CCR5, on monocytes in a time-dependent manner. Taken together, our data indicate that HIV-1 Tat may facilitate the recruitment of monocytes into the CNS by inducing MCP-1 expression in astrocytes. These recruited monocytes may contribute to the pathogenesis of HIV-1-associated AIDS encephalitis and dementia.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Weiss
authors.forename: A
authors.initials: A
authors.lastname: Nath
authors.forename: E O
authors.initials: EO
authors.lastname: Major
authors.forename: J W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D001812:Blood-Brain Barrier / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000502:physiology*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005333:Fetus; D015696:Gene Products, tat / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: C515334:CCR2 protein, human; D018932:Chemokine CCL2; D015696:Gene Products, tat; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D054322:tat Gene Products, Human Immunodeficiency Virus