Transport of lipoprotein lipase across endothelial cells.
Lipoprotein lipase (LPL), synthesized in muscle and fat, hydrolyzes plasma triglycerides primarily while bound to luminal endothelial cell surfaces. To obtain information about the movement of LPL from the basal to the luminal endothelial cell surface, we studied the transport of purified bovine milk LPL across bovine aortic endothelial cell monolayers. 125I-labeled LPL (125I-LPL) added to the basal surface of the monolayers was detected on the apical side of the cells in two compartments: (i) in the medium of the upper chamber, and (ii) bound to the apical cell surface. The amount of 125I-LPL on the cell surface, but not in the medium, reached saturation with time and LPL dose. Catalytically active LPL was transported to the apical surface but very little LPL activity appeared in the medium. Heparinase treatment of the basal cell surface and addition of dextran sulfate (0.15 microM) to the lower chamber decreased the amount of 125I-LPL appearing on the apical surface. Similarly, the presence of increasing molar ratios of oleic acid/bovine serum albumin at the basal surface decreased the transport of active LPL across the monolayer. Thus, a saturable transport system, which requires heparan sulfate proteoglycans and is inhibited by high concentrations of free fatty acids on the basal side of the cells, appears to exist for passage of enzymatically active LPL across endothelial cells. We postulate that regulation of LPL transport to the endothelial luminal surface modulates the physiologically active pool of LPL in vivo.
Saxena
U
U
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Klein
M G
MG
Goldberg
I J
IJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000302:isolation & purification / Q000378:metabolism*; D008892:Milk / Q000201:enzymology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D009829:Oleic Acids; D012710:Serum Albumin, Bovine; D019301:Oleic Acid; D008071:Lipoprotein Lipase