Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth 
in vitro, is angiogenic in vivo

Fràter-Schröder, M; Riesau, W; Hallmann, R; Gautschi, P; Böhlen, P

doi:10.1073/pnas.84.15.5277

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Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo

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Riesau, W
Department Physical Biology, Max Planck Institute for Developmental Biology, Max Planck Society;

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Hallmann, R
Department Physical Biology, Max Planck Institute for Developmental Biology, Max Planck Society;

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Citation

Fràter-Schröder, M., Riesau, W., Hallmann, R., Gautschi, P., & Böhlen, P. (1987). Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proceedings of the National Academy of Sciences of the United States of America, 84(15), 5277-5281. doi:10.1073/pnas.84.15.5277.

Cite as: https://hdl.handle.net/21.11116/0000-000E-5A71-E

Abstract

Tumor necrosis factor type alpha (TNF-alpha) inhibits endothelial cell proliferation in vitro. Basal cell growth (in the absence of exogenously added growth factor) and fibroblast growth factor (FGF)-stimulated cell proliferation are inhibited in a dose-dependent manner from 0.1 to 10 ng/ml with half-maximal inhibition occurring at 0.5-1.0 ng of TNF-alpha per ml. Bovine aortic and brain capillary endothelial and smooth muscle cells are similarly affected. TNF-alpha is a noncompetitive antagonist of FGF-stimulated cell proliferation. Its action on endothelial cells is reversible and noncytotoxic. Surprisingly, TNF-alpha does not seem to inhibit endothelial cell proliferation in vivo. In the rabbit cornea, even a high dose of TNF-alpha (10 micrograms) does not suppress angiogenesis induced by basic FGF. On the contrary, in this model system TNF-alpha stimulates neovascularization. The inflammatory response that is seen in the cornea after TNF-alpha implantation suggests that the angiogenic properties of this agent may be a consequence of leukocyte infiltration.