Rapid disruption of an astrocyte interaction with the extracellular matrix mediated by integrin alpha 6 beta 4 during focal cerebral ischemia/reperfusion - PubMed (original) (raw)

Rapid disruption of an astrocyte interaction with the extracellular matrix mediated by integrin alpha 6 beta 4 during focal cerebral ischemia/reperfusion

S Wagner et al. Stroke. 1997 Apr.

Abstract

Background and purpose: Integrins participate in cerebral microvascular integrity and signaling during focal ischemia/ reperfusion. The integrin subunits alpha 1, alpha 6, and beta 1 are distributed identically on normal cerebral microvessels. Studies in epithelium indicate that integrin alpha 6 beta 4, which interacts with laminin-5 in the basal lamina/extracellular matrix, is unique. This study describes the exact location of alpha 6, beta 4, and alpha 6 beta 4 and that their responses in focal cerebral ischemia are relevant to astrocyte-matrix interactions.

Methods: The effect of middle cerebral artery occlusion and subsequent reperfusion on the microvascular expression of alpha 6 beta 4 and laminin-5 in regions of cellular injury (dUTP incorporation) was examined in 15 nonhuman primates. Well-characterized antibodies against human alpha 6, beta 4, alpha 6 beta 4, laminin-5 and laminin-1, endothelial CD31, and vascular markers were measured with computerized video imaging and laser confocal microscopy.

Results: Integrin alpha 6 beta 4 was localized on astrocytes where it connects with the extracellular matrix at the astrocyte-vessel interface. It represented 59.3 +/- 16.4% of alpha 6 antigen in cerebral microvessels < 100 microns in diameter. By 2 hours of ischemia, the significant reduction in alpha 6 expression (2P < .001) was accompanied by decreases in beta 4/laminin-5 (0.76 +/- 0.03 to 0.20 +/- 0.09; 2P = .001) and alpha 6 beta 4/laminin-5 (0.73 +/- 0.18 to 0.25 +/- 0.11; 2P = .001) in the region of dUTP incorporation. Parallel changes in laminin-5 and laminin-1 were less pronounced and coincided by 24 hours.

Conclusions: This is the first description of a potential role of integrin alpha 6 beta 4 in the brain, where it mediates astrocyte-matrix interactions. The dramatic disappearance of alpha 6 beta 4 relative to its ligands reflects early loss of integrity between the astrocyte and the vessel wall in selected microvessels in response to ischemia.

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