Linked Life Data

17065217

Source:http://linkedlifedata.com/resource/pubmed/id/17065217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2006-12-4
pubmed:abstractText
The blood-brain barrier (BBB), a selective barrier formed by endothelial cells and dependent on the presence of tight junctions, is compromised during neuroinflammation. A detailed study of tight junction dynamics during transendothelial migration of leukocytes has been lacking. Therefore, we retrovirally expressed green fluorescent protein (GFP) fused to the N-terminus of the tight junction protein occludin in the rat brain endothelial cell line GP8/3.9. Confocal microscopy analyses revealed that GFP-occludin colocalized with the intracellular tight junction protein, ZO-1, localized at intercellular connections, and was absent at cell borders lacking apposing cells. Using live cell imaging we found that monocytes scroll over the brain endothelial cell surface toward cell-cell contacts, induce gap formation, which is associated with local disappearance of GFP-occludin, and subsequently traverse the endothelium paracellularly. Immunoblot analyses indicated that loss of occludin was due to protein degradation. The broad spectrum matrix metalloproteinase (MMP) inhibitor BB-3103 significantly inhibited endothelial gap formation, occludin loss, and the ability of monocytes to pass the endothelium. Our results provide a novel insight into the mechanism by which leukocytes traverse the BBB and illustrate that therapeutics aimed at the stabilization of the tight junction may be beneficial to resist a neuroinflammatory attack.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2550-2
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Diapedesis of monocytes is associated with MMP-mediated occludin disappearance in brain endothelial cells.
pubmed:affiliation
Neuroimmunology Research Group, Molecular Cell Biology and Immunology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. a.reijerkerk@vumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't