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Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo

Standard

Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. / Broermann, Andre; Winderlich, Mark; Block, Helena; Frye, Maike; Rossaint, Jan; Zarbock, Alexander; Cagna, Giuseppe; Linnepe, Ruth; Schulte, Dörte; Nottebaum, Astrid Fee; Vestweber, Dietmar.

in: J EXP MED, Jahrgang 208, Nr. 12, 21.11.2011, S. 2393-401.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Broermann, A, Winderlich, M, Block, H, Frye, M, Rossaint, J, Zarbock, A, Cagna, G, Linnepe, R, Schulte, D, Nottebaum, AF & Vestweber, D 2011, 'Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo', J EXP MED, Jg. 208, Nr. 12, S. 2393-401. https://doi.org/10.1084/jem.20110525

APA

Broermann, A., Winderlich, M., Block, H., Frye, M., Rossaint, J., Zarbock, A., Cagna, G., Linnepe, R., Schulte, D., Nottebaum, A. F., & Vestweber, D. (2011). Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. J EXP MED, 208(12), 2393-401. https://doi.org/10.1084/jem.20110525

Vancouver

Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A et al. Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. J EXP MED. 2011 Nov 21;208(12):2393-401. https://doi.org/10.1084/jem.20110525

Bibtex

@article{b50dbde2a0a8407b9c958b10f8102034,
title = "Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo",
abstract = "We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation.",
keywords = "Animals, Antigens, CD/metabolism, COS Cells, Cadherins/metabolism, Capillary Permeability/physiology, Chlorocebus aethiops, DNA Primers/genetics, Endothelial Cells/metabolism, Gene Knock-In Techniques, Immunoblotting, Immunoprecipitation, Leukocytes/physiology, Lipopolysaccharides, Lung/metabolism, Mice, Pneumonia/immunology, Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism, Recombinant Fusion Proteins/metabolism, Tacrolimus/metabolism, Transendothelial and Transepithelial Migration/physiology, Vascular Endothelial Growth Factor A/metabolism",
author = "Andre Broermann and Mark Winderlich and Helena Block and Maike Frye and Jan Rossaint and Alexander Zarbock and Giuseppe Cagna and Ruth Linnepe and D{\"o}rte Schulte and Nottebaum, {Astrid Fee} and Dietmar Vestweber",
year = "2011",
month = nov,
day = "21",
doi = "10.1084/jem.20110525",
language = "English",
volume = "208",
pages = "2393--401",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo

AU - Broermann, Andre

AU - Winderlich, Mark

AU - Block, Helena

AU - Frye, Maike

AU - Rossaint, Jan

AU - Zarbock, Alexander

AU - Cagna, Giuseppe

AU - Linnepe, Ruth

AU - Schulte, Dörte

AU - Nottebaum, Astrid Fee

AU - Vestweber, Dietmar

PY - 2011/11/21

Y1 - 2011/11/21

N2 - We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation.

AB - We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation.

KW - Animals

KW - Antigens, CD/metabolism

KW - COS Cells

KW - Cadherins/metabolism

KW - Capillary Permeability/physiology

KW - Chlorocebus aethiops

KW - DNA Primers/genetics

KW - Endothelial Cells/metabolism

KW - Gene Knock-In Techniques

KW - Immunoblotting

KW - Immunoprecipitation

KW - Leukocytes/physiology

KW - Lipopolysaccharides

KW - Lung/metabolism

KW - Mice

KW - Pneumonia/immunology

KW - Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism

KW - Recombinant Fusion Proteins/metabolism

KW - Tacrolimus/metabolism

KW - Transendothelial and Transepithelial Migration/physiology

KW - Vascular Endothelial Growth Factor A/metabolism

U2 - 10.1084/jem.20110525

DO - 10.1084/jem.20110525

M3 - SCORING: Journal article

C2 - 22025303

VL - 208

SP - 2393

EP - 2401

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 12

ER -