title: ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood-brain barrier.
abstract: Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to mediate leukocyte migration across the blood-brain barrier (BBB) in multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). Here, we confirmed vascular ALCAM expression in human brain tissue samples in situ and on two different human in vitro BBB models. Antibody-mediated inhibition of ALCAM reduced diapedesis of human CD4+Th1 but not of Th17 cells across the human BBB in vitro. In accordance to human Th1 cells, mouse Th1 cells showed reduced diapedesis across an ALCAM-/-in vitro BBB model under static but no longer under flow conditions. In contrast to the limited role of ALCAM in T cell extravasation across the BBB, we found a contribution of ALCAM to rolling, adhesion, and diapedesis of human CD14+monocytes across the human BBB under flow and static conditions. Taken together, our study highlights the potential differences in the CNS expression of ALCAM in mouse and human and supports a prominent role for ALCAM in the multi-step extravasation of monocytes across the BBB.
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lyck
authors.affiliation: 2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Neuroimmunology Research Laboratory, Montréal, Québec, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Lécuyer
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Abadier
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Christof B
authors.initials: CB
authors.lastname: Wyss
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Matti
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rosito
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Enzmann
authors.affiliation: 3 Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeis
authors.affiliation: 2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Neuroimmunology Research Laboratory, Montréal, Québec, Canada.
authors.forename: Laure
authors.initials: L
authors.lastname: Michel
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Ana B
authors.initials: AB
authors.lastname: García Martín
authors.affiliation: 4 Institute for Research in Biomedicine, Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: 5 Sciences Faculty Jean Perrin, Artois University, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.affiliation: 6 Departments of Biology and Psychiatry, The University of Iowa, Iowa City, IA, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Weiner
authors.affiliation: 3 Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaeren-Wiemers
authors.affiliation: 2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Neuroimmunology Research Laboratory, Montréal, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: 1 Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology* / Q000502:physiology; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule
keywords: ALCAM; blood–brain barrier; immune cell extravasation; multiple sclerosis; neuroinflammation