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Tissue factor production by cultured rat mesangial cells. Stimulation by TNF alpha and lipopolysaccharide
R C Wiggins1, N Njoku, J R Sedor
1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Abstract:
Fibrin formation plays an important role in glomerular injury. We therefore examined the procoagulant signal produced by cultured rat mesangial cells. Actively growing mesangial cells produced procoagulant activity (PCA) that was present in intact cells (surface-associated), was inhibitable by cyclohexamide and which, by clotting assay, had the characteristics of tissue factor. This PCA decreased with incubation of cells in serum-deprived medium. Incubation with bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) induced increased detectable tissue factor by mesangial cells within two hours which was maximal by four hours. We conclude that quiescent mesangial cells produce a small amount of tissue factor-like procoagulant activity, and that this PCA can be stimulated by incubation with TNF alpha, LPS or when cells are actively growing in high serum medium. Therefore mesangial cells have the capability of contributing to fibrin formation during inflammatory glomerular injury or sepsis.
Insights
Rat mesangial cells generate tissue factor, a procoagulant activity. This activity, crucial in glomerular injury, increases with inflammation and cell growth.
Area of Science:
- Nephrology
- Hematology
- Cell Biology
Background:
- Fibrin formation is a key factor in glomerular injury.
- Mesangial cells are integral components of the glomerulus.
Purpose of the Study:
- To investigate the procoagulant signal produced by cultured rat mesangial cells.
- To determine the role of mesangial cells in fibrin formation during glomerular injury.
Main Methods:
- Cultured rat mesangial cells were used to assess procoagulant activity (PCA).
- Clotting assays were performed to characterize PCA as tissue factor.
- Cells were incubated with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α) to evaluate stimulation.
Main Results:
- Actively growing mesangial cells exhibited surface-associated PCA with tissue factor characteristics.
- PCA decreased in serum-deprived conditions.
- LPS and TNF-α significantly increased detectable tissue factor within 4 hours.
Conclusions:
- Quiescent mesangial cells produce a basal level of tissue factor-like PCA.
- PCA production is stimulated by TNF-α, LPS, and active cell growth in high serum.
- Mesangial cells can contribute to fibrin formation in inflammatory conditions like glomerular injury and sepsis.