title: Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system.
abstract: Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.
authors.affiliation: Neuroimmunology Research Laboratory, Center for Excellence in Neuromics, Centre Hospitalier de l'Université de Montréal-Notre-Dame Hospital, Université de Montréal, H2L 4M1, Montréal, Québec, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Cayrol
authors.forename: Karolina
authors.initials: K
authors.lastname: Wosik
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Berard
authors.forename: Aurore
authors.initials: A
authors.lastname: Dodelet-Devillers
authors.forename: Igal
authors.initials: I
authors.lastname: Ifergan
authors.forename: Hania
authors.initials: H
authors.lastname: Kebir
authors.forename: Arsalan S
authors.initials: AS
authors.lastname: Haqqani
authors.forename: Katharina
authors.initials: K
authors.lastname: Kreymborg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Krug
authors.forename: Robert
authors.initials: R
authors.lastname: Moumdjian
authors.forename: Alain
authors.initials: A
authors.lastname: Bouthillier
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
authors.forename: Samuel
authors.initials: S
authors.lastname: David
authors.forename: Danica
authors.initials: D
authors.lastname: Stanimirovic
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule