Title | Exposure of human astrocytes to leukotriene C4 promotes a CX3CL1/fractalkine-mediated transmigration of HIV-1-infected CD4⁺ T cells across an in vitro blood-brain barrier model. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Auteurs | Bertin, J, Jalaguier, P, Barat, C, Roy, M-A, Tremblay, MJ |
Journal | Virology |
Volume | 454-455 |
Pagination | 128-38 |
Date Published | 2014 Apr |
ISSN | 1096-0341 |
Keywords | Astrocytes, Blood-Brain Barrier, CD4-Positive T-Lymphocytes, Cell Movement, Cells, Cultured, Chemokine CX3CL1, Culture Media, Conditioned, Endothelial Cells, HIV-1, Humans, Leukotriene C4 |
Abstract | Eicosanoids, including cysteinylleukotrienes (cysLTs), are found in the central nervous system (CNS) of individuals infected with HIV-1. Few studies have addressed the contribution of cysLTs in HIV-1-associated CNS disorders. We demonstrate that conditioned medium from human astrocytes treated with leukotriene C4 (LTC4) increases the transmigration of HIV-1-infected CD4(+) T cells across an in vitro blood-brain barrier (BBB) model using cultured brain endothelial cells. Additional studies indicate that the higher cell migration is linked with secretion by astrocytes of CX3CL1/fractalkine, a chemokine that has chemoattractant activity for CD4(+) T cells. Moreover, we report that the enhanced cell migration across BBB leads to a more important CD4(+) T cell-mediated HIV-1 transfer toward macrophages. Altogether data presented in the present study reveal the important role that LTC4, a metabolite of arachidonic acid, may play in the HIV-1-induced neuroinvasion, neuropathogenesis and disease progression. |
DOI | 10.1016/j.virol.2014.02.007 |
Alternate Journal | Virology |
PubMed ID | 24725939 |
Grant List | HET-85519 / / Canadian Institutes of Health Research / Canada |