title: Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue.
abstract: The mechanisms by which chronic ethanol (EtOH) consumption results in an immune-compromised state have not been fully elucidated. No studies to date have ascertained whether EtOH affects the migratory capacity of dendritic cells (DC), potent immune regulators. We hypothesized that EtOH exposure might affect hepatic and splenic DC trafficking to secondary lymphoid tissues and the resulting immune response. Hepatic DC from EtOH-treated animals migrated in greater numbers to draining lymphoid tissue than controls, whereas spleen DC were unaffected. Moreover, hepatic EtOH-exposed (E) DC induced more vigorous priming of allogeneic T cells in vivo compared with splenic EDC or controls. Altered hepatic EDC migration was independent of either CCR7 or CD11a expression, with no striking changes in surface expression of other adhesion molecules analyzed. The modified trafficking to secondary lymphoid tissue observed for hepatic EDC may play a role in the altered immune response to microbial pathogens in chronic alcohol users.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Audrey H
authors.initials: AH
authors.lastname: Lau
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Colvin
mesh_terms: D020751:Alcohol-Induced Disorders / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens / Q000096:biosynthesis / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D000431:Ethanol; D037181:Lectins, C-Type; D009838:Oligodeoxyribonucleotides; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C515371:Ccr7 protein, mouse; C513201:CpG-B 2006