INTEGRIN RECEPTORS AND FUNCTION ON CULTURED GLOMERULAR ENDOTHELIAL-CELLS

Integrin expression and function on a cloned line of rat glomerular endothelial cells (GEndoC) were studied in an effort to obtain a better understanding of the means by which these cells interact with components of the glomerular basement membrane. Cultured GEndoC adhered to fibronectin, laminin and types I and IV collagen and expressed alpha1beta1, alpha2beta1, alpha3beta1, alpha5beta1, alpha(v)beta1 and alpha(v)beta3 integrins. Synthetic RGDS peptides significantly decreased adhesion to fibronectin (53.1 +/- 4.7% of control). Antibody to rat beta1 integrin strongly inhibited adhesion to laminin, fibronectin and types I and IV collagen (I 1.2, 19.0, 67.3 and 31.9% of control adhesion, respectively), while antibody to the rat a, integrin chain strongly inhibited adhesion to laminin (65.2% of control), but only mildly inhibited adhesion to type IV collagen (77.2% of control) and did not affect adhesion to type I collagen (97.8% of control). Affinity chromatography of GEndoC lysates on a column of immobilized type I collagen displayed predominantly binding of alpha3beta1 integrin with trace amounts of alpha1beta1, and alpha2beta1, documenting the major role of alpha3beta1, in GEndoC adhesion to collagen. Chromatography on the immobilized cell-binding fragment of fibronectin revealed the alpha5beta1 integrin to be the major fibronectin receptor on these cells, but antibody to alpha(v)beta3 integrin also documented a minor role for alpha(v)beta1 or alpha(v)beta3 in fibronectin adhesion. Cultured GEndoC express a similar array of integrin receptors in vitro as they do in vivo. Further study of the function of these receptors in normal and diseased glomeruli may provide important insights into the pathogenesis of disease states characterized by endothelial detachment or subendothelial protein deposition.