ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier

Ruth Lyck; Marc-André Lécuyer; Michael Abadier; Christof Wyss; Christoph Matti; Maria Rosito; Gaby Enzmann; Thomas Zeis; Laure Michel; Ana García Martín; Federica Sallusto; Fabien Gosselet; Urban Deutsch; Joshua Weiner; Nicole Schaeren-Wiemers; Alexandre Prat; Britta Engelhardt

doi:10.1177/0271678X16678639

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ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier

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ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier

Ruth Lyck, Marc-André Lécuyer, Michael Abadier, Christof Wyss, Christoph Matti, Maria Rosito, Gaby Enzmann, Thomas Zeis, Laure Michel, Ana García Martín, …

Journal of cerebral blood flow and metabolism, Vol.37(8), pp.2894-2909

08/2017

DOI: 10.1177/0271678X16678639

PMCID: PMC5536797

PMID: 28273717

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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.

Life Sciences

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Title: Subtitle: ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier
Creators: Ruth Lyck - Theodor Kocher Institute
Marc-André Lécuyer - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Michael Abadier - Theodor Kocher Institute
Christof Wyss - Theodor Kocher Institute
Christoph Matti - Theodor Kocher Institute
Maria Rosito - Theodor Kocher Institute
Gaby Enzmann - Theodor Kocher Institute
Thomas Zeis - University Hospital Basel [Basel]
Laure Michel - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Ana García Martín - Theodor Kocher Institute
Federica Sallusto - Institute for Research in Biomedicine
Fabien Gosselet - Laboratoire de la Barrière Hémato-Encéphalique
Urban Deutsch - Theodor Kocher Institute
Joshua Weiner - University of Iowa [Iowa City]
Nicole Schaeren-Wiemers - University Hospital Basel [Basel]
Alexandre Prat - Centre de Recherche du Centre Hospitalier de l’Université de Montréal
Britta Engelhardt - Theodor Kocher Institute
Resource Type: Journal article
Publication Details: Journal of cerebral blood flow and metabolism, Vol.37(8), pp.2894-2909
DOI: 10.1177/0271678X16678639
PMID: 28273717
PMCID: PMC5536797
NLM abbreviation: J Cereb Blood Flow Metab
ISSN: 0271-678X
eISSN: 1559-7016
Publisher: Nature Publishing Group
Language: English
Date published: 08/2017
Academic Unit: Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
Record Identifier: 9983997436902771

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