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PMID: 3598461 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 166 ·No. 1 ·1987-07-01 ·Pages 235-45

Hajjar KA, Hajjar DP, Silverstein RL, Nachman RL

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.

MeSH Terms
Cell Division Cells, Cultured Dactinomycin/pharmacology Endothelium/drug effects,metabolism Glycoproteins/pharmacology Humans Kinetics Muscle, Smooth, Vascular/cytology,metabolism Platelet-Derived Growth Factor/genetics,metabolism RNA, Messenger/biosynthesis Tumor Necrosis Factor-alpha Umbilical Veins
Chemicals
Glycoproteins Platelet-Derived Growth Factor RNA, Messenger Tumor Necrosis Factor-alpha Dactinomycin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hajjar K A
Hajjar D P
Silverstein R L
Nachman R L
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45 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.166.1.235
Published
1987-07-01
Pages
235-45
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188629
Subset
IM
Grants
NHLBI NIH HHS · HL-01352 · United States
NHLBI NIH HHS · HL-18828 · United States
NHLBI NIH HHS · HL-35564 · United States
External Links
PubMed source DOI: 10.1084/jem.166.1.235 PMC Full Text View journal details
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