Endothelial injury is a prominent feature of the adult respiratory distress syndrome (ARDS). Manifestations of the endothelial cell response to acute lung injury include increased capillary permeability and remodelling of the pulmonary vascular bed which result in the exposure of endothelial cells to various components of the extracellular matrix (ECM). Cells interact with the ECM through a variety of adhesion receptors, many of which are integrins. This project aims to further characterize the structure and function of two novel endothelial cell integrin alpha subunits, provisionally designated as alphaB1 and alphaB2, recently identified by Dr. Schnapp using homology PCR. Library screening and homology PCR will be used to obtain the complete sequences of alphaB1 and alphaB2. Concurrently, tissue distribution of these molecules will be investigated using Northern analysis and in situ hybridization. Northern analysis will also be used to investigate the regulation of expression of alphaB1 and alphaB2 by cytokines known to be important in the processes of endothelial injury and repair. Once the complete sequences of alphabeta1 and alphabeta2 are determined, antibodies will be made against the cytoplasmic domain to obtain information about beta subunit partners and ligands using immunoprecipitation and affinity chromatography. These studies should provide new information regarding the interactions of endothelial cells with extracellular matrix proteins and/or other cells. The experiments will be done at the Lung Biology Center at San Francisco General Hospital. The Lung Biology Center provides a unique environment for the integration of the clinical and basic science aspects of pulmonary medicine and is equipped with all facilities necessary to perform this project.
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