Albumin uptake and transcytosis in endothelial cells in vivo induced by albumin-binding protein

The 60-kDa endothelial cell surface albumin-binding glycoprotein (gp60) is postulated to be a docking site for albumin that mediates the uptake of alb umin and its transport in cultured microvessel endothelial cells. In the pr esent study, we used an isolated Krebs-perfused rat lung preparation to add ress the in vivo role of gp60 in mediating albumin uptake and transport. Ad dition of primary anti-gp60 antibody to the perfusate followed by the secon dary antibody to cross-link gp60 increased the vessel wall I-125-albumin pe rmeability-surface area (PS) product 2.5-fold without affecting the capilla ry filtration coefficient (K-f,K-c; a measure of liquid permeability). In c ontrast, EDTA (5 mM), which induces interendothelial gap formation, produce d parallel increases in both K-f,K-c and I-125-albumin PS product. Increasi ng perfusate albumin concentration to >1 g/100 ml (EC50 1.2 g/100 ml) was s ufficient to block I-125-albumin PS product, indicating that the perfusate albumin competed with tracer albumin for transendothelial albumin transport . Cross-linking of gp60 in lungs perfused with saturating concentration of albumin resulted in a greater increase in I-125-albumin PS product, indicat ing that gp60 function was capable of being modulated. These results show t hat activation of gp60 in pulmonary microvessels induces albumin uptake and its transport through a nonhydraulic pathway that fits with a model of alb umin permeability via the transcellular pathway.