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Cayrol, Romain; Wosik, Karolina; Berard, Jennifer L; Dodelet-Devillers, Aurore; Ifergan, Igal; Kebir, Hania; Haqqani, Arsalan S; Kreymborg, Katharina; Krug, Sebastian; Moumdjian, Robert; Bouthillier, Alain; Becher, Burkhard; Arbour, Nathalie; David, Samuel; Stanimirovic, Danica; Prat, Alexandre (2008). Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nature Immunology, 9(2):137-45.

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Abstract

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.

Citations

138 citations in Web of Science®
157 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:19 Jun 2012 14:42
Last Modified:27 Nov 2013 19:41
Publisher:Nature Publishing Group
ISSN:1529-2908
Publisher DOI:10.1038/ni1551
PubMed ID:18157132

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