Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis.

Lécuyer, Marc-André; Saint-Laurent, Olivia; Bourbonnière, Lyne; Larouche, Sandra; Larochelle, Catherine; Michel, Laure; Charabati, Marc; Abadier, Michael Magdy Labib; Zandee, Stephanie; Haghayegh Jahromi, Neda; Gowing, Elizabeth; Pittet, Camille; Lyck, Ruth; Engelhardt, Britta; Prat, Alexandre (2017). Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 114(4), E524-E533. National Academy of Sciences NAS 10.1073/pnas.1614336114

[img] Text
PNAS-2017-Lécuyer-E524-33.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

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.

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:

Abadier, Michael Magdy Labib; Haghayegh Jahromi, Neda; Lyck, Ruth and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

11 Sep 2017 14:45

Last Modified:

11 Sep 2017 14:55

Publisher DOI:

10.1073/pnas.1614336114

PubMed ID:

28069965

Uncontrolled Keywords:

ALCAM EAE blood–brain barrier multiple sclerosis tight junctions

BORIS DOI:

10.7892/boris.95397

URI:

https://boris.unibe.ch/id/eprint/95397

Actions (login required)

Edit item Edit item
Provide Feedback