This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (33)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Multiple Sclerosis/ Demyelinating Disease  • Immunologic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Alexandre Prat, MD, PhD; Katarzyna Biernacki, MSc; Jean-Francois Lavoie, BSc; Josee Poirier, B Inf; Pierre Duquette, MD; Jack P. Antel, MD

Arch Neurol. 2002;59:391-397.

Context  T-lymphocyte migration through the blood-brain barrier is a central event in the process of lesion formation in multiple sclerosis (MS).

Objectives  To assess the ability of lymphocytes derived from the peripheral blood of patients with clinically active and inactive MS to migrate across an artificial model of the blood-brain barrier and to elucidate the molecular mechanisms involved in such a process.

Design  We developed an in vitro model of lymphocyte migration using a Boyden chamber coated with a monolayer of human brain microvascular endothelial cells.

Results  The rates of migration of lymphocytes obtained from patients with acutely relapsing and active secondary progressive MS was significantly increased compared with those obtained from healthy controls and patients with inactive secondary progressive disease. Ribonuclease protection assays and enzyme-linked immunosorbent assays indicated that monocyte chemoattractant protein 1 and interleukin 8 were the major chemokines produced by brain endothelial cells grown under the culture conditions used for the migration assays. The rate of migration of the MS lymphocytes could be inhibited by 60% with an antimonocyte chemoattractant protein 1 monoclonal antibody, indicating a functional role for this chemokine in the migration process. In agreement with previous reports, we found that the tissue inhibitor of metalloproteinase 1, a matrix metalloproteinase inhibitor, also reduced migration of MS lymphocytes by 50%.

Conclusions  The results demonstrate an increased migration rate of MS T lymphocytes across the brain endothelium barrier and that such migration is dependent on chemokine monocyte chemoattractant protein 1 and on matrix metalloproteinases.

From the Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec (Drs Prat and Antel, Mss Biernacki and Poirier, and Mr Lavoie); and the Department of Neurology, Hopital Nôtre-Dame, Université de Montréal, Montréal (Drs Prat and Duquette).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2002;59(3):492-494.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Peripheral blood CD4+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line
Bahbouhi et al.
J. Leukoc. Biol. 2009;86:1049-1063.
ABSTRACT | FULL TEXT  

The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells
Ifergan et al.
Brain 2008;131:785-799.
ABSTRACT | FULL TEXT  

Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis: An Open-Label Trial
Minagar et al.
Arch Neurol 2008;65:199-204.
ABSTRACT | FULL TEXT  

Angiotensin II Controls Occludin Function and Is Required for Blood Brain Barrier Maintenance: Relevance to Multiple Sclerosis
Wosik et al.
J. Neurosci. 2007;27:9032-9042.
ABSTRACT | FULL TEXT  

Metalloproteinases Control Brain Inflammation Induced by Pertussis Toxin in Mice Overexpressing the Chemokine CCL2 in the Central Nervous System
Toft-Hansen et al.
J. Immunol. 2006;177:7242-7249.
ABSTRACT | FULL TEXT  

Elevated endothelial microparticle--monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-{beta}1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes
Jimenez et al.
Mult Scler 2005;11:310-315.
ABSTRACT  

Interferon Beta Promotes Nerve Growth Factor Secretion Early in the Course of Multiple Sclerosis
Biernacki et al.
Arch Neurol 2005;62:563-568.
ABSTRACT | FULL TEXT  

LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in neutrophils
Zhou et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 2005;288:L655-L662.
ABSTRACT | FULL TEXT  

Determinants of Human B Cell Migration Across Brain Endothelial Cells
Alter et al.
J. Immunol. 2003;170:4497-4505.
ABSTRACT | FULL TEXT  

Granulocyte-Macrophage Colony-Stimulating Factor Induces an Expression Program in Neonatal Microglia That Primes Them for Antigen Presentation
Re et al.
J. Immunol. 2002;169:2264-2273.
ABSTRACT | FULL TEXT