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.

ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier / Lyck, R.; Lecuyer, M. -A.; Abadier, M.; Wyss, C. B.; Matti, C.; Rosito, M.; Enzmann, G.; Zeis, T.; Michel, L.; Garcia Martin, A. B.; Sallusto, F.; Gosselet, F.; Deutsch, U.; Weiner, J. A.; Schaeren-Wiemers, N.; Prat, A.; Engelhardt, B.. - In: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. - ISSN 0271-678X. - 37:8(2017), pp. 1-16. [10.1177/0271678X16678639]

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

Rosito M.;Gosselet F.;
2017

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.
2017
alcam; blood–brain barrier; immune cell extravasation; multiple sclerosis; neuroinflammation; animals; antigens; cd; blood-brain barrier; cell adhesion molecules; neuronal; cells; cultured; encephalomyelitis; autoimmune; experimental; endothelial cells; endothelium; vascular; fetal proteins; humans; mice; inbred c57bl; mice; knockout; monocytes; multiple sclerosis; t-lymphocytes; transendothelial and transepithelial migration
01 Pubblicazione su rivista::01a Articolo in rivista
ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier / Lyck, R.; Lecuyer, M. -A.; Abadier, M.; Wyss, C. B.; Matti, C.; Rosito, M.; Enzmann, G.; Zeis, T.; Michel, L.; Garcia Martin, A. B.; Sallusto, F.; Gosselet, F.; Deutsch, U.; Weiner, J. A.; Schaeren-Wiemers, N.; Prat, A.; Engelhardt, B.. - In: JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. - ISSN 0271-678X. - 37:8(2017), pp. 1-16. [10.1177/0271678X16678639]
File allegati a questo prodotto
File Dimensione Formato  
Lyck_ALCAM-CD166_2016.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.37 MB
Formato Adobe PDF
1.37 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1608970
Citazioni
  • ???jsp.display-item.citation.pmc??? 37
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 48
social impact