title: Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis.
abstract: Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls. Passive EAE transfer experiments suggested that the pathophysiology observed in active EAE was linked to the absence of ALCAM on BBB-ECs. In addition, phenotypic characterization of unimmunized ALCAM KO mice revealed a reduced expression of BBB junctional proteins. Further in vivo, in vitro, and molecular analysis confirmed that ALCAM is associated with tight junction molecule assembly at the BBB, explaining the increased permeability of CNS blood vessels in ALCAM KO animals. Collectively, our data point to a biologically important function of ALCAM in maintaining BBB integrity.
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Marc-André
authors.identifier: 0000-0003-0465-6122
authors.initials: MA
authors.lastname: Lécuyer
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Olivia
authors.initials: O
authors.lastname: Saint-Laurent
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Lyne
authors.initials: L
authors.lastname: Bourbonnière
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Sandra
authors.initials: S
authors.lastname: Larouche
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Catherine
authors.initials: C
authors.lastname: Larochelle
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Laure
authors.initials: L
authors.lastname: Michel
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Marc
authors.initials: M
authors.lastname: Charabati
authors.affiliation: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Abadier
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zandee
authors.affiliation: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
authors.forename: Neda
authors.initials: N
authors.lastname: Haghayegh Jahromi
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gowing
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9.
authors.forename: Camille
authors.initials: C
authors.lastname: Pittet
authors.affiliation: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lyck
authors.affiliation: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.affiliation: Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada H2X 0A9; a.prat@umontreal.ca.|Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada H3T 1J4.
authors.forename: Alexandre
authors.identifier: 0000-0001-6188-0580
authors.initials: A
authors.lastname: Prat
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000378:metabolism; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D062725:Tight Junction Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: ALCAM; EAE; blood–brain barrier; multiple sclerosis; tight junctions