A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability

Matthias Clauss, Cord Sunderkötter, Baldur Sveinbjörnsson, Stefan Hippenstiel, Antje Willuweit, Michael Marino, Elvira Haas, Rolf Seljelid, Peter Scheurich, Norbert Suttorp, Matthias Grell, Werner Risau

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) induces both angiogenesis and an increase in vascular permeability, 2 processes that are considered to be important for both tumor growth and the delivery of drugs to the site of tumors. This study demonstrates that transmembrane expression of tumor necrosis factor (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is also present on cultivated human endothelial cells. It is further shown that tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in vivo. This permissive activity of TNF appears to be selective, because anti-TNF antibodies ablated the VEGF-induced permeability but not proliferation of cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no obvious defects in vascularization and develop normally but failed to respond to administration of VEGF with an increase in vascular permeability. Subsequent studies indicated that the tmTNF and VEGF signaling pathways converge at the level of a secondary messenger, the "stress-activated protein kinase-2" (SAPK-2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38 activation abolished the vascular permeability activity of VEGF in vivo. In conclusion, the study's finding that continuous autocrine signaling by tmTNF sensitizes endothelial cells to respond to VEGF by increasing their vascular permeability provides new therapeutic concepts for manipulating vascular hyperpermeability.

Original languageEnglish (US)
Pages (from-to)1321-1329
Number of pages9
JournalBlood
Volume97
Issue number5
DOIs
StatePublished - Mar 1 2001
Externally publishedYes

Fingerprint

Capillary Permeability
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha
Mitogen-Activated Protein Kinase 11
Endothelial cells
Endothelial Cells
Tumors
Chemical activation
Autocrine Communication
Methylcholanthrene
Sarcoma
Endothelium
Blood Vessels
Anti-Idiotypic Antibodies
Permeability
Neoplasms
Genes
Skin
Defects
Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

Clauss, M., Sunderkötter, C., Sveinbjörnsson, B., Hippenstiel, S., Willuweit, A., Marino, M., ... Risau, W. (2001). A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability. Blood, 97(5), 1321-1329. https://doi.org/10.1182/blood.V97.5.1321

A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability. / Clauss, Matthias; Sunderkötter, Cord; Sveinbjörnsson, Baldur; Hippenstiel, Stefan; Willuweit, Antje; Marino, Michael; Haas, Elvira; Seljelid, Rolf; Scheurich, Peter; Suttorp, Norbert; Grell, Matthias; Risau, Werner.

In: Blood, Vol. 97, No. 5, 01.03.2001, p. 1321-1329.

Research output: Contribution to journalArticle

Clauss, M, Sunderkötter, C, Sveinbjörnsson, B, Hippenstiel, S, Willuweit, A, Marino, M, Haas, E, Seljelid, R, Scheurich, P, Suttorp, N, Grell, M & Risau, W 2001, 'A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability', Blood, vol. 97, no. 5, pp. 1321-1329. https://doi.org/10.1182/blood.V97.5.1321
Clauss M, Sunderkötter C, Sveinbjörnsson B, Hippenstiel S, Willuweit A, Marino M et al. A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability. Blood. 2001 Mar 1;97(5):1321-1329. https://doi.org/10.1182/blood.V97.5.1321
Clauss, Matthias ; Sunderkötter, Cord ; Sveinbjörnsson, Baldur ; Hippenstiel, Stefan ; Willuweit, Antje ; Marino, Michael ; Haas, Elvira ; Seljelid, Rolf ; Scheurich, Peter ; Suttorp, Norbert ; Grell, Matthias ; Risau, Werner. / A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability. In: Blood. 2001 ; Vol. 97, No. 5. pp. 1321-1329.
@article{6fac8e2c09aa4508b10599cf54a6c81e,
title = "A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability",
abstract = "Vascular endothelial growth factor (VEGF) induces both angiogenesis and an increase in vascular permeability, 2 processes that are considered to be important for both tumor growth and the delivery of drugs to the site of tumors. This study demonstrates that transmembrane expression of tumor necrosis factor (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is also present on cultivated human endothelial cells. It is further shown that tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in vivo. This permissive activity of TNF appears to be selective, because anti-TNF antibodies ablated the VEGF-induced permeability but not proliferation of cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no obvious defects in vascularization and develop normally but failed to respond to administration of VEGF with an increase in vascular permeability. Subsequent studies indicated that the tmTNF and VEGF signaling pathways converge at the level of a secondary messenger, the {"}stress-activated protein kinase-2{"} (SAPK-2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38 activation abolished the vascular permeability activity of VEGF in vivo. In conclusion, the study's finding that continuous autocrine signaling by tmTNF sensitizes endothelial cells to respond to VEGF by increasing their vascular permeability provides new therapeutic concepts for manipulating vascular hyperpermeability.",
author = "Matthias Clauss and Cord Sunderk{\"o}tter and Baldur Sveinbj{\"o}rnsson and Stefan Hippenstiel and Antje Willuweit and Michael Marino and Elvira Haas and Rolf Seljelid and Peter Scheurich and Norbert Suttorp and Matthias Grell and Werner Risau",
year = "2001",
month = "3",
day = "1",
doi = "10.1182/blood.V97.5.1321",
language = "English (US)",
volume = "97",
pages = "1321--1329",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - A permissive role for tumor necrosis factor in vascular endothelial growth factor-induced vascular permeability

AU - Clauss, Matthias

AU - Sunderkötter, Cord

AU - Sveinbjörnsson, Baldur

AU - Hippenstiel, Stefan

AU - Willuweit, Antje

AU - Marino, Michael

AU - Haas, Elvira

AU - Seljelid, Rolf

AU - Scheurich, Peter

AU - Suttorp, Norbert

AU - Grell, Matthias

AU - Risau, Werner

PY - 2001/3/1

Y1 - 2001/3/1

N2 - Vascular endothelial growth factor (VEGF) induces both angiogenesis and an increase in vascular permeability, 2 processes that are considered to be important for both tumor growth and the delivery of drugs to the site of tumors. This study demonstrates that transmembrane expression of tumor necrosis factor (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is also present on cultivated human endothelial cells. It is further shown that tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in vivo. This permissive activity of TNF appears to be selective, because anti-TNF antibodies ablated the VEGF-induced permeability but not proliferation of cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no obvious defects in vascularization and develop normally but failed to respond to administration of VEGF with an increase in vascular permeability. Subsequent studies indicated that the tmTNF and VEGF signaling pathways converge at the level of a secondary messenger, the "stress-activated protein kinase-2" (SAPK-2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38 activation abolished the vascular permeability activity of VEGF in vivo. In conclusion, the study's finding that continuous autocrine signaling by tmTNF sensitizes endothelial cells to respond to VEGF by increasing their vascular permeability provides new therapeutic concepts for manipulating vascular hyperpermeability.

AB - Vascular endothelial growth factor (VEGF) induces both angiogenesis and an increase in vascular permeability, 2 processes that are considered to be important for both tumor growth and the delivery of drugs to the site of tumors. This study demonstrates that transmembrane expression of tumor necrosis factor (tmTNF) is up-regulated in the endothelium of a murine methylcholanthrene (meth A)-induced sarcoma in comparison to the adjacent normal dermal vasculature and is also present on cultivated human endothelial cells. It is further shown that tmTNF is required for VEGF-mediated endothelial hyperpermeability in vitro and in vivo. This permissive activity of TNF appears to be selective, because anti-TNF antibodies ablated the VEGF-induced permeability but not proliferation of cultivated human endothelial cells. Furthermore, tnf gene-deficient mice show no obvious defects in vascularization and develop normally but failed to respond to administration of VEGF with an increase in vascular permeability. Subsequent studies indicated that the tmTNF and VEGF signaling pathways converge at the level of a secondary messenger, the "stress-activated protein kinase-2" (SAPK-2)/p38: (1) up-regulated endothelial expression of tmTNF resulted in the continuous activation of SAPK-2/p38 in vitro, and (2) an inhibitor of SAPK-2/p38 activation abolished the vascular permeability activity of VEGF in vivo. In conclusion, the study's finding that continuous autocrine signaling by tmTNF sensitizes endothelial cells to respond to VEGF by increasing their vascular permeability provides new therapeutic concepts for manipulating vascular hyperpermeability.

UR - http://www.scopus.com/inward/record.url?scp=0035282925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035282925&partnerID=8YFLogxK

U2 - 10.1182/blood.V97.5.1321

DO - 10.1182/blood.V97.5.1321

M3 - Article

C2 - 11222376

AN - SCOPUS:0035282925

VL - 97

SP - 1321

EP - 1329

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -