Document Detail


The blood-brain barrier, chemokines and multiple sclerosis.
MedLine Citation:
PMID:  20692338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The infiltration of leukocytes into the central nervous system (CNS) is an essential step in the neuropathogenesis of multiple sclerosis (MS). Leukocyte extravasation from the bloodstream is a multistep process that depends on several factors including fluid dynamics within the vasculature and molecular interactions between circulating leukocytes and the vascular endothelium. An important step in this cascade is the presence of chemokines on the vascular endothelial cell surface. Chemokines displayed along the endothelial lumen bind chemokine receptors on circulating leukocytes, initiating intracellular signaling that culminates in integrin activation, leukocyte arrest, and extravasation. The presence of chemokines at the endothelial lumen can help guide the movement of leukocytes through peripheral tissues during normal immune surveillance, host defense or inflammation. The expression and display of homeostatic or inflammatory chemokines therefore critically determine which leukocyte subsets extravasate and enter the peripheral tissues. Within the CNS, however, infiltrating leukocytes that cross the endothelium face additional boundaries to parenchymal entry, including the abluminal presence of localizing cues that prevent egress from perivascular spaces. This review focuses on the differential display of chemokines along endothelial surfaces and how they impact leukocyte extravasation into parenchymal tissues, especially within the CNS. In particular, the display of chemokines by endothelial cells of the blood brain barrier may be altered during CNS autoimmune disease, promoting leukocyte entry into this immunologically distinct site. Recent advances in microscopic techniques, including two-photon and intravital imaging have provided new insights into the mechanisms of chemokine-mediated capture of leukocytes within the CNS.
Authors:
David W Holman; Robyn S Klein; Richard M Ransohoff
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-08-06
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1812     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-03-01     Revised Date:  2012-02-02    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  220-30     Citation Subset:  IM    
Copyright Information:
2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / immunology,  physiology*
Cell Movement
Chemokines / immunology,  physiology*
Endothelium / immunology,  physiology
Humans
Immunity, Innate
Leukocytes / immunology,  physiology
Lymphoid Tissue / immunology,  physiology
Models, Immunological
Models, Neurological
Multiple Sclerosis / etiology*,  immunology
Receptors, Chemokine / immunology,  physiology
Grant Support
ID/Acronym/Agency:
P01 NS059560-020002/NS/NINDS NIH HHS; R01 NS052632-07/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Receptors, Chemokine

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