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.
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.
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec - pavillon CHUL, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bertin
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec - pavillon CHUL, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Jalaguier
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec - pavillon CHUL, Canada.
authors.forename: Corinne
authors.initials: C
authors.lastname: Barat
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec - pavillon CHUL, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Roy
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec - pavillon CHUL, Canada; Département de Microbiologie-Infectiologie et Immunologie, Faculté de médecine, Université Laval, Québec, Canada. Electronic address: michel.j.tremblay@crchul.ulaval.ca.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D001253:Astrocytes / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D002465:Cell Movement; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000502:physiology*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism*
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D017077:Culture Media, Conditioned; D017997:Leukotriene C4
keywords: Blood–brain barrier; Central nervous system; HIV-1; Leukotrienes