Inhibition of endothelial cell proliferation by gamma-interferon.
Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen for endothelial cells and fibroblasts. The mitogenic effects of ECGF are inhibited by the lymphokine gamma-interferon (gamma-IFN) in a dose-dependent manner. Gamma-IFN also induces a unique change in endothelial cell morphology which is maximally expressed in the presence of ECGF. The antiproliferative and phenotypic modulatory effects of gamma-IFN on endothelial cells are reversible. Inhibition of ECGF-induced endothelial cell proliferation by gamma-IFN is accompanied by a concentration- and time-dependent decrease in binding of 125I-ECGF to the endothelial cell surface. Scatchard analyses of the binding data in the presence and absence of gamma-IFN demonstrate a decrease in the number of ECGF-binding sites rather than a decrease in ligand affinity for the receptor. Cross-linking experiments with disuccinimidyl suberate demonstrate a decrease in the 170,000 Mr cross-linked receptor-ligand complex. These data suggest that gamma-IFN inhibits endothelial cell proliferation by a mechanism which involves growth factor receptor modulation.
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016228:Endothelial Growth Factors; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007700:Kinetics; D011975:Receptors, Mitogen / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins
D016228:Endothelial Growth Factors; D006133:Growth Substances; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D007371:Interferon-gamma; D040262:Receptors, Vascular Endothelial Growth Factor