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 albumin and its transport in cultured microvessel endothelial cells. In the present study, we used an isolated Krebs-perfused rat lung preparation to address the in vivo role of gp60 in mediating albumin uptake and transport. Addition of primary anti-gp60 antibody to the perfusate followed by the secondary antibody to cross-link gp60 increased the vessel wall (125)I-albumin permeability-surface area (PS) product 2.5-fold without affecting the capillary filtration coefficient (K(f,c;) a measure of liquid permeability). In contrast, EDTA (5 mM), which induces interendothelial gap formation, produced parallel increases in both K(f,c) and (125)I-albumin PS product. Increasing perfusate albumin concentration to >1 g/100 ml (EC(50) 1.2 g/100 ml) was sufficient to block (125)I-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 (125)I-albumin PS product, indicating that gp60 function was capable of being modulated. These results show that activation of gp60 in pulmonary microvessels induces albumin uptake and its transport through a non-hydraulic pathway that fits with a model of albumin permeability via the transcellular pathway.
Vogel
S M
SM
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA. vogel@uic.edu
Minshall
R D
RD
Pilipović
M
M
Tiruppathi
C
C
Malik
A B
AB
D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005372:Filipin / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008168:Lung / Q000098:blood supply*; D051381:Rats
D000418:Albumins; D000900:Anti-Bacterial Agents; D000906:Antibodies; D003432:Cross-Linking Reagents; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D005372:Filipin