Inhibition of junctional adhesion molecule-A/LFA interaction attenuates leukocyte trafficking and inflammation in brain ischemia/reperfusion injury.
Neurobiol Dis
; 67: 57-70, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24657919
ABSTRACT
Proinflammatory mediators trigger intensive postischemic inflammatory remodeling of the blood-brain barrier (BBB) including extensive brain endothelial cell surface and junctional complex changes. Junctional adhesion molecule-A (JAM-A) is a component of the brain endothelial junctional complex with dual roles paracellular route occlusion and regulating leukocyte docking and migration. The current study examined the contribution of JAM-A to the regulation of leukocyte (neutrophils and monocytes/macrophages) infiltration and the postischemic inflammatory response in brain ischemia/reperfusion (I/R injury). Brain I/R injury was induced by transient middle cerebral artery occlusion (MCAO) for 30min in mice followed by reperfusion for 0-5days, during which time JAM-A antagonist peptide (JAM-Ap) was administered. The peptide, which inhibits JAM-A/leukocyte interaction by blocking the interaction of the C2 domain of JAM-A with LFA on neutrophils and monocytes/macrophages, attenuated I/R-induced neutrophil and monocyte infiltration into brain parenchyma. Consequently, mice treated with JAM-A peptide during reperfusion had reduced expression (~3-fold) of inflammatory mediators in the ischemic penumbra, reduced infarct size (94±39 vs 211±38mm3) and significantly improved neurological score. BBB hyperpermeability was also reduced. Collectively, these results indicate that JAM-A has a prominent role in regulating leukocyte infiltration after brain I/R injury and could be a new target in limiting post-ischemic inflammation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Movimento Celular
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Isquemia Encefálica
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Encefalite
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Molécula A de Adesão Juncional
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Leucócitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article