Transvascular protein transport in mice lacking endothelial caveolae.
(2006) In American Journal of Physiology: Heart and Circulatory Physiology 291(3). p.1371-1377- Abstract
- Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO (n=12) and male control mice (n=13) were intubated and anesthetized using 2% isoflurane. I-125-labeled albumin, I-131-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and... (More)
- Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO (n=12) and male control mice (n=13) were intubated and anesthetized using 2% isoflurane. I-125-labeled albumin, I-131-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and permeability-surface area product for glucose were assessed. Transvascular protein transport was higher in Cav-1-KO compared with control mice. Albumin clearance from plasma to peritoneum was 0.088 +/- 0.008 mu l/min in control and 0.179 +/- 0.012 mu l/min in Cav-1-KO (P = 0.001) mice. IgM clearance was 0.049 +/- 0.003 and 0.083 +/- 0.010 mu l/min in control and Cav-1-KO mice, respectively (P = 0.016). Ficoll clearance was increased in Cav-1-KO mice. In conclusion, the lack of caveolae in Cav-1-KO mice resulted in a marked increase in macromolecular transport. A two-pore analysis of the Ficoll clearance data revealed that the higher transport rate in Cav-1-KO mice was not compatible with the appearance of an alternative pathway for macromolecular transport. In contrast, the higher transperitoneal protein and Ficoll clearance is consistent with passive porous transport through an unperturbed two-pore system, presumably at an elevated capillary hydraulic pressure. Alternatively, the data may be explained by reductions in the selectivity of the endothelial glycocalyx, leading to an increased capillary hydraulic conductivity and large solute filtration. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/153353
- author
- Rosengren, Bert-Inge LU ; Rippe, Anna LU ; Rippe, Catarina LU ; Venturoli, Daniele LU ; Swärd, Karl LU and Rippe, Bengt LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- macromolecules, pores, permeability, vesicles, transcytosis
- in
- American Journal of Physiology: Heart and Circulatory Physiology
- volume
- 291
- issue
- 3
- pages
- 1371 - 1377
- publisher
- American Physiological Society
- external identifiers
-
- pmid:16501011
- wos:000239680000044
- scopus:33748426207
- ISSN
- 1522-1539
- DOI
- 10.1152/ajpheart.01364.2005
- language
- English
- LU publication?
- yes
- id
- e4f50758-eb4e-4ebf-a464-032f75e031f8 (old id 153353)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16501011&dopt=Abstract
- date added to LUP
- 2016-04-01 12:36:05
- date last changed
- 2022-03-29 03:08:32
@article{e4f50758-eb4e-4ebf-a464-032f75e031f8,
abstract = {{Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO (n=12) and male control mice (n=13) were intubated and anesthetized using 2% isoflurane. I-125-labeled albumin, I-131-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and permeability-surface area product for glucose were assessed. Transvascular protein transport was higher in Cav-1-KO compared with control mice. Albumin clearance from plasma to peritoneum was 0.088 +/- 0.008 mu l/min in control and 0.179 +/- 0.012 mu l/min in Cav-1-KO (P = 0.001) mice. IgM clearance was 0.049 +/- 0.003 and 0.083 +/- 0.010 mu l/min in control and Cav-1-KO mice, respectively (P = 0.016). Ficoll clearance was increased in Cav-1-KO mice. In conclusion, the lack of caveolae in Cav-1-KO mice resulted in a marked increase in macromolecular transport. A two-pore analysis of the Ficoll clearance data revealed that the higher transport rate in Cav-1-KO mice was not compatible with the appearance of an alternative pathway for macromolecular transport. In contrast, the higher transperitoneal protein and Ficoll clearance is consistent with passive porous transport through an unperturbed two-pore system, presumably at an elevated capillary hydraulic pressure. Alternatively, the data may be explained by reductions in the selectivity of the endothelial glycocalyx, leading to an increased capillary hydraulic conductivity and large solute filtration.}},
author = {{Rosengren, Bert-Inge and Rippe, Anna and Rippe, Catarina and Venturoli, Daniele and Swärd, Karl and Rippe, Bengt}},
issn = {{1522-1539}},
keywords = {{macromolecules; pores; permeability; vesicles; transcytosis}},
language = {{eng}},
number = {{3}},
pages = {{1371--1377}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Heart and Circulatory Physiology}},
title = {{Transvascular protein transport in mice lacking endothelial caveolae.}},
url = {{https://lup.lub.lu.se/search/files/2989954/625328.pdf}},
doi = {{10.1152/ajpheart.01364.2005}},
volume = {{291}},
year = {{2006}},
}