The goal of Project 1 is to define the function of the recently identified albumin-binding 60 kDa glycoprotein (gp60) on the endothelial cell surface in mediating increased vascular endothelial permeability. We have purified gp60 from bovine pulmonary microvessel endothelial cell (BPMVEC) membranes and human lung tissue. Cross-linking of gp60 using an anti-gp60 antibody (Ab) and secondary Ab increased the uptake and transport of 125 I-labeled albumin 2- to 3-fold without an increase in liquid permeability. Studies have co-localized gp60 with caveolin-surface gp60 with its ligand, albumin, stimulated the internalization of gp60 in caveolae. These results have led to the hypothesis that albumin-binding to the endothelial cell surface gp60 mediates the internalization and transcytosis of albumin. Project 1 will (1) identify the albumin binding domains of gp60 and their amino acid sequences; (2) determine the in vitro and in vivo effects of gp60 activation on the endothelial barrier function; (3) study the interactions of gp60 with caveolin-1 and members of Src tyrosine kinases and determine the G-protein transduction pathways intervening between albumin binding and the membrane dynamics that regulate endothelial permeability; (4) determine the function of gp60 in mediating albumin permeability by cloning gp60 and studying its expression; and (5) determine the role of gp60 in mediating states of increased pulmonary vascular endothelial permeability. With the achievement of these aims, we will provide new insights into the role of gp60 in regulating endothelial permeability via the transcellular pathway.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Illinois at Chicago
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