Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules

1. Integrin-mediated endothelial cell-extracellular matrix adhesion plays a critical role in maintaining the structural integrity of microvascular wal ls. The aim of this study was to evaluate the impact of specific integrin e xtracellular domain binding to matrix fibronectin and vitronectin on the ba rrier function of intact microvascular endothelium. 2. The apparent permeability coefficient of albumin was measured in isolate d and perfused porcine coronary venules using a fluorescence ratioing techn ique with the aid of fluorescence microscopy. Inhibition of integrin bindin g to either fibronectin with GRGDdSP peptide or vitronectin with GPenGRGDSP CA peptide dose-dependently increased venular permeability by 2- to 3-fold. The effects were sustained for more than 60 min and were reversible upon c learance of the peptides. In contrast, the inactive control peptide GRADSP did not significantly affect venular permeability. Pretreatment of the venu les with purified human fibronectin and vitronectin, respectively, prevente d the hyperpermeability response to GRGDdSP and GPenGRGDSPCA. 3. GRGDSP, a peptide that inhibits integrin binding to both fibronectin and vitronectin, produced an even higher permeability (4.5-fold) in venules th an GRGDdSP or GPenGRGDSPCA alone, and the effect was blunted in vessels pre incubated with both fibronectin and vitronectin. 4. The results indicate the importance of integrin-matrix interaction in th e physiological regulation of microvascular permeability. It is likely that both fibronectin and vitronectin binding to integrins contribute to the ma intenance of endothelial barrier function in venules.