Attachment of primary neonatal rat astrocytes to vitronectin is mediated by integrins alpha v beta 5 and alpha 8 beta 1: modulation by the type 1 plasminogen activator inhibitor

Vitronectin is expressed in a cell-specific manner in the developing brain and concentrated in the brain during disease processes, such as germinal ma trix hemorrhage and infarction, in which there is breakdown of the blood-br ain barrier. In this study, we identified the integrin receptors that media te attachment of primary neonatal rat astrocytes to vitronectin. Using fluo rescent activated cell sorter and immunoprecipitation analyses, we establis hed that the vitronectin receptor integrins alpha v beta 5 and alpha 8 beta 1, but not alpha v beta 3, are expressed on neonatal rat astrocytes. Attac hment of the neonatal astrocytes to vitronectin was inhibited (85%) in an a dditive manner by neutralizing anti-alpha v beta 5 and anti-beta 1 antibodi es. Attachment to vitronectin was also inhibited in a dose-dependent manner by the type I plasminogen activator inhibitor (PAI-1), a serine protease i nhibitor. Our data demonstrate that unstimulated primary neonatal rat astro cytes attach to vitronectin, utilizing integrins alpha v beta 5 and alpha 8 beta 1, and that this attachment is regulated by PAI-1. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.