Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo.
The role of endothelial cell caveolae in the uptake and transport of macromolecules from the blood-space to the tissue-space remains controversial. To address this issue directly, we employed caveolin-1 gene knock-out mice that lack caveolin-1 protein expression and caveolae organelles. Here, we show that endothelial cell caveolae are required for the efficient uptake and transport of a known caveolar ligand, i.e. albumin, in vivo. Caveolin-1-null mice were perfused with 5-nm gold-conjugated albumin, and its uptake was followed by transmission electron microscopy. Our results indicate that gold-conjugated albumin is not endocytosed by Cav-1-deficient lung endothelial cells and remains in the blood vessel lumen; in contrast, gold-conjugated albumin was concentrated and internalized by lung endothelial cell caveolae in wild-type mice, as expected. To quantitate this defect in uptake, we next studied the endocytosis of radioiodinated albumin using aortic ring segments from wild-type and Cav-1-null mice. Interestingly, little or no uptake of radioiodinated albumin was observed in the aortic segments from Cav-1-deficient mice, whereas aortic segments from wild-type mice showed robust uptake that was time- and temperature-dependent and competed by unlabeled albumin. We conclude that endothelial cell caveolae are required for the efficient uptake and transport of albumin from the blood to the interstitium.
Schubert
W
W
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Frank
P G
PG
Razani
B
B
Park
D S
DS
Chow
C W
CW
Lisanti
M P
MP
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology*; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics* / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D017979:Gold Colloid / Q000378:metabolism; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000378:metabolism; D008168:Lung; D051379:Mice; D018345:Mice, Knockout
D000418:Albumins; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D017979:Gold Colloid; D007457:Iodine Radioisotopes