Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo

William Schubert, Philippe G. Frank, Babak Razani, David S. Park, Chi Wing Chow, Michael P. Lisanti

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)48619-48622
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number52
DOIs
StatePublished - Dec 28 2001

Fingerprint

Caveolae
Endothelial cells
Albumins
Endothelial Cells
Defects
Caveolin 1
Gold
Endocytosis
Blood
Caveolins
Lung
Gene Knockout Techniques
Blood vessels
Transmission Electron Microscopy
Macromolecules
Knockout Mice
Organelles
Blood Vessels
Genes
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Schubert, W., Frank, P. G., Razani, B., Park, D. S., Chow, C. W., & Lisanti, M. P. (2001). Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo. Journal of Biological Chemistry, 276(52), 48619-48622. https://doi.org/10.1074/jbc.C100613200

Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo. / Schubert, William; Frank, Philippe G.; Razani, Babak; Park, David S.; Chow, Chi Wing; Lisanti, Michael P.

In: Journal of Biological Chemistry, Vol. 276, No. 52, 28.12.2001, p. 48619-48622.

Research output: Contribution to journalArticle

Schubert, W, Frank, PG, Razani, B, Park, DS, Chow, CW & Lisanti, MP 2001, 'Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo', Journal of Biological Chemistry, vol. 276, no. 52, pp. 48619-48622. https://doi.org/10.1074/jbc.C100613200
Schubert, William ; Frank, Philippe G. ; Razani, Babak ; Park, David S. ; Chow, Chi Wing ; Lisanti, Michael P. / Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 52. pp. 48619-48622.
@article{09cf15a8e06446b79b818723521c6153,
title = "Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo",
abstract = "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.",
author = "William Schubert and Frank, {Philippe G.} and Babak Razani and Park, {David S.} and Chow, {Chi Wing} and Lisanti, {Michael P.}",
year = "2001",
month = "12",
day = "28",
doi = "10.1074/jbc.C100613200",
language = "English (US)",
volume = "276",
pages = "48619--48622",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "52",

}

TY - JOUR

T1 - Caveolae-deficient Endothelial Cells Show Defects in the Uptake and Transport of Albumin in Vivo

AU - Schubert, William

AU - Frank, Philippe G.

AU - Razani, Babak

AU - Park, David S.

AU - Chow, Chi Wing

AU - Lisanti, Michael P.

PY - 2001/12/28

Y1 - 2001/12/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035965995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035965995&partnerID=8YFLogxK

U2 - 10.1074/jbc.C100613200

DO - 10.1074/jbc.C100613200

M3 - Article

C2 - 11689550

AN - SCOPUS:0035965995

VL - 276

SP - 48619

EP - 48622

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 52

ER -