title: Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFα in macrophages.
abstract: The presence of human immunodeficiency virus (HIV)-infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome-related neuroinflammation. Once penetrated the blood-brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell-cell interaction between HIV-infected macrophages and astrocytes, we observed that the HIV-1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP-1 chemokine in astroglial cells isolated from HIV-1-infected co-cultures compared with cells from uninfected co-cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell-cell contact. In addition, it was a consequence of the HIV-1-induced enhancement of membrane-associated tumor necrosis factor-α in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV-infected patients.
authors.affiliation: National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Muratori
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mangino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Affabris
authors.forename: Maurizio
authors.initials: M
authors.lastname: Federico
mesh_terms: D001253:Astrocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D001254:Astrocytoma; D001932:Brain Neoplasms; D002450:Cell Communication / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology; D018920:Coculture Techniques; D015870:Gene Expression / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D020411:Oligonucleotide Array Sequence Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D020298:U937 Cells
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D008565:Membrane Proteins; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha