Transvascular protein transport in mice lacking endothelial caveolae.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Transvascular protein transport in mice lacking endothelial caveolae. / Rosengren, Bert-Inge; Rippe, Anna; Rippe, Catarina; Venturoli, Daniele; Swärd, Karl; Rippe, Bengt.

I: American Journal of Physiology: Heart and Circulatory Physiology, Vol. 291, Nr. 3, 2006, s. H1371-H1377.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

CBE

MLA

Vancouver

Author

Rosengren, Bert-Inge ; Rippe, Anna ; Rippe, Catarina ; Venturoli, Daniele ; Swärd, Karl ; Rippe, Bengt. / Transvascular protein transport in mice lacking endothelial caveolae. I: American Journal of Physiology: Heart and Circulatory Physiology. 2006 ; Vol. 291, Nr. 3. s. H1371-H1377.

RIS

TY - JOUR

T1 - Transvascular protein transport in mice lacking endothelial caveolae.

AU - Rosengren, Bert-Inge

AU - Rippe, Anna

AU - Rippe, Catarina

AU - Venturoli, Daniele

AU - Swärd, Karl

AU - Rippe, Bengt

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - macromolecules

KW - pores

KW - permeability

KW - vesicles

KW - transcytosis

U2 - 10.1152/ajpheart.01364.2005

DO - 10.1152/ajpheart.01364.2005

M3 - Article

VL - 291

SP - H1371-H1377

JO - American Journal of Physiology - Heart and Circulatory Physiology

T2 - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 1522-1539

IS - 3

ER -