|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|
|Authors||Bertin, J, Jalaguier, P, Barat, C, Roy, M-A, Tremblay, MJ|
|Date Published||2014 Apr|
|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|
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.
|Grant List||HET-85519 / / Canadian Institutes of Health Research / Canada|