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

Lyck, Ruth; Lécuyer, Marc-André; Abadier, Michael Magdy Labib; Wyss, Christof B.; Matti, Christoph; Rosito, Maria; Enzmann, Gaby; Zeis, Thomas; Michel, Laure; Garcia Martin, Ana Bélen; Sallusto, Federica; Gosselet, Fabien; Deutsch, Urban; Weiner, Joshua A.; Schaeren-Wiemers, Nicole; Prat, Alexandres; Engelhardt, Britta (2017). ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier. Journal of cerebral blood flow and metabolism, 37(8), pp. 2894-2909. Nature Publishing Group 10.1177/0271678X16678639

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Lyck, Ruth; Abadier, Michael Magdy Labib; Rosito, Maria; Enzmann, Gaby; Garcia Martin, Ana Bélen; Deutsch, Urban and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0271-678X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 13:30

Last Modified:

30 Jul 2017 01:30

Publisher DOI:

10.1177/0271678X16678639

PubMed ID:

28273717

Uncontrolled Keywords:

ALCAM; blood–brain barrier; immune cell extravasation; multiple sclerosis; neuroinflammation

BORIS DOI:

10.7892/boris.95374

URI:

https://boris.unibe.ch/id/eprint/95374

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