title: Lymphocyte adhesion to CCR5 ligands is reduced by anti-CCR5 gene delivery.
abstract: Immune-mediated damage to the central nervous system (CNS) is an important contributor to many CNS diseases, including epilepsy. Chemokines play a role in leukocyte recruitment to, and migration across, the blood-brain barrier (BBB) during many such processes. We previously investigated the role of the chemokine receptor CCR5 in a rat model of epilepsy based on intraperitoneal kainic acid (KA) administration. Before KA injection, rats were given intramarrow inoculations of SV(RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi) that targets CCR5. Decreased CCR5 expression in blood cells after vector administration reduced expression of CCR5 ligands MIP-1α and RANTES in the microvasculature, and strongly protected from BBB leakage, CNS loss and inflammation and facilitated CNS repair. We show here that rSV40-mediated downregulation of CCR5 in lymphocytes decreased cellular adhesion to surfaces carrying CCR5 ligands. These data suggest that reducing CCR5 in peripheral blood mononuclear cells (PBMCs) might alter their adhesion to the microvasculature and their participation in inflammatory processes.
authors: Department of Pathology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA.
authors: Elena
authors: E
authors: Marusich
authors: Jean-Pierre
authors: JP
authors: Louboutin
authors: Alena A
authors: AA
authors: Chekmasova
authors: David S
authors: DS
authors: Strayer
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology / Q000821:virology; D065100:CCR5 Receptor Antagonists; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004827:Epilepsy / Q000276:immunology / Q000473:pathology / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000821:virology; D008024:Ligands; D016131:Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D065100:CCR5 Receptor Antagonists; D008024:Ligands; D012367:RNA, Viral; D019713:Receptors, CCR5