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J. Biol. Chem., Vol. 276, Issue 52, 48619-48622, December 28, 2001
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§,§
,§**,§,, and§¶
From the 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.
Department of Molecular Pharmacology and
the § Division of Hormone-dependent Tumor
Biology at The Albert Einstein Comprehensive Cancer Center, Albert
Einstein College of Medicine, Bronx, New York 10461
Supported by Postdoctoral Fellowships from the Heart and
Stroke Foundation of Canada and the Canadian Institutes of Health Research.
**
Supported by National Institutes of Health Medical Scientist
Training Grant T32-GM07288.
Supported by National Institutes of Health Graduate Training
Program Grant TG-CA09475.
¶
To whom correspondence should be addressed: Dept. of Molecular
Pharmacology, The Albert Einstein College of Medicine, 1300 Morris Park
Ave., Rm. 202, Golding Bldg., Bronx, NY 10461. Tel.: 718-430-8828; Fax:
718-430-8830; E-mail: lisanti@aecom.yu.edu.
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