Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells.

TitleTumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells.
Publication TypeJournal Article
Year of Publication1987
AuthorsHajjar KA, Hajjar DP, Silverstein RL, Nachman RL
JournalJ Exp Med
Volume166
Issue1
Pagination235-45
Date Published1987 Jul 01
ISSN0022-1007
KeywordsCell Division, Cells, Cultured, Dactinomycin, Endothelium, Glycoproteins, Humans, Kinetics, Muscle, Smooth, Vascular, Platelet-Derived Growth Factor, RNA, Messenger, Tumor Necrosis Factor-alpha, Umbilical Veins
Abstract

Platelet-derived growth factor (PDGF) is a 30,000-Mr glycoprotein that is chemotactic and mitogenic for vascular smooth muscle cells (SMC). It is also a potent vasoconstrictor. In the present study, we found that the macrophage-derived polypeptide, tumor necrosis factor (TNF), releases a factor from human umbilical vein endothelial cells (EC) that is mitogenic for SMC. Postculture medium from TNF-stimulated EC induced a 90% increase in mitogenesis is compared with controls. This effect was half-maximal at a TNF dose of 114 pM, reflected a 2.5-fold increase in PDGF-specific mRNA synthesis, and peaked at 15 h of TNF stimulation. Mitogenic activity was completely abrogated by preincubation of postculture medium with antibody to platelet PDGF. Stimulation of EC with IL-1 (60-240 pM) led to the release of similar mitogenic activity. Thus, in addition to its effects on the hemostatic and adhesive properties of EC, TNF also promotes release of PDGF, which may serve to modulate proliferation of vascular SMC during wound healing, inflammation, and atherogenesis.

DOI10.1084/jem.166.1.235
Alternate JournalJ Exp Med
PubMed ID3598461
PubMed Central IDPMC2188629
Grant ListHL-01352 / HL / NHLBI NIH HHS / United States
HL-18828 / HL / NHLBI NIH HHS / United States
HL-35564 / HL / NHLBI NIH HHS / United States
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David P. Hajjar, Ph.D.

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