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Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells
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.
Insights
Tumor necrosis factor (TNF) stimulates endothelial cells to release platelet-derived growth factor (PDGF), promoting vascular smooth muscle cell (SMC) proliferation. This finding is crucial for understanding SMC growth in conditions like wound healing and atherosclerosis.
Area of Science:
- Cell Biology
- Immunology
- Vascular Biology
Background:
- Platelet-derived growth factor (PDGF) is a glycoprotein mitogenic for vascular smooth muscle cells (SMC).
- Tumor necrosis factor (TNF) is a macrophage-derived polypeptide with various biological activities.
Purpose of the Study:
- To investigate if TNF can induce the release of SMC-mitogenic factors from endothelial cells (EC).
- To determine the role of PDGF in TNF-induced SMC proliferation.
Main Methods:
- Stimulation of human umbilical vein endothelial cells (EC) with TNF.
- Measurement of SMC mitogenesis in postculture medium.
- Quantification of PDGF-specific mRNA synthesis.
- Abrogation of mitogenic activity using anti-PDGF antibody.
Main Results:
- TNF-stimulated EC released a factor that increased SMC mitogenesis by 90%.
- This effect was dose-dependent on TNF and peaked at 15 hours.
- The mitogenic activity was neutralized by antibody to PDGF, confirming PDGF release.
- Interleukin-1 (IL-1) also induced similar mitogenic activity release from EC.
Conclusions:
- TNF promotes the release of PDGF from EC, which stimulates SMC proliferation.
- This mechanism may play a role in vascular SMC modulation during wound healing, inflammation, and atherogenesis.
- TNF influences EC beyond hemostasis and adhesion, impacting vascular SMC growth.