Faculty Collaboration Database

Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J Exp Med 1987 Jul 01;166(1):235-45

Date

07/01/1987

Pubmed ID

3598461

Pubmed Central ID

PMC2188629

DOI

10.1084/jem.166.1.235

Scopus ID

2-s2.0-0023257296 (requires institutional sign-in at Scopus site)   155 Citations

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.

Author List

Hajjar KA, Hajjar DP, Silverstein RL, Nachman RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Division
Cells, Cultured
Dactinomycin
Endothelium
Glycoproteins
Humans
Kinetics
Muscle, Smooth, Vascular
Platelet-Derived Growth Factor
RNA, Messenger
Tumor Necrosis Factor-alpha
Umbilical Veins