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Effect of concanavalin A on nephrotic peripheral blood mononuclear cells mediated increased 35sulfate uptake in rat
Abstract:
We have previously shown a significant increase in 35sulfate uptake in rat glomerular basement membrane (GBM) when glomeruli were cocultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse, but an uptake not different than normal controls if glomeruli were incubated with PBMC of patients in remission. In the present study we examined 35sulfate uptake by GBM after PBMC from 12 IMLNS patients in remission were stimulated with Concanavalin A (Con A) (10 micrograms/ml of culture media). There was a significant increase in 35sulfate GBM uptake when glomeruli were cocultured with Con A-stimulated IMLNS PBMC (geometric mean), 331 cpm/mg dry glomerular weight) as compared to glomeruli cocultured with IMLNS PBMC (geometric mean, 200) (p = 0.048); glomeruli alone stimulated with Con A (geometric mean, 182) (p = 0.008) or glomeruli alone (geometric mean, 146) (p = 0.002). No significant differences were seen between the groups when glomeruli were cocultured with PBMC from 12 normal adults. These data show that Con A stimulated PBMC from IMLNS patients in remission alter the sulfate metabolism of rat GBM. The stimulation of PBMC with Con A reproduces the increase in 35sulfate uptake observed when glomeruli are cocultured with PBMC from IMLNS in relapse. Sulfated compounds in the GBM may play a role in glomerular permeability. Since stimulated nephrotic PBMC alter the metabolism of GBM sulfated compounds, these findings may have pathogenic significance.
Insights
Peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in remission, when stimulated, increase sulfate uptake in the glomerular basement membrane (GBM). This suggests a role for sulfated compounds in GBM permeability and potential pathogenic significance in IMLNS.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Previous studies showed increased 35sulfate uptake in rat glomerular basement membrane (GBM) with peripheral blood mononuclear cells (PBMC) from idiopathic minimal lesion nephrotic syndrome (IMLNS) patients in relapse.
- However, PBMC from IMLNS patients in remission did not alter GBM sulfate uptake compared to controls.
Purpose of the Study:
- To investigate if stimulating PBMC from IMLNS patients in remission with Concanavalin A (Con A) alters 35sulfate uptake in rat GBM.
- To explore the role of sulfated compounds in GBM permeability and their potential pathogenic significance in IMLNS.
Main Methods:
- Cocultured rat glomeruli with PBMC from 12 IMLNS patients in remission, either unstimulated or stimulated with Con A (10 micrograms/ml).
- Measured 35sulfate uptake in GBM using scintillation counting.
- Included control groups: glomeruli alone and glomeruli with Con A alone.
Main Results:
- Con A-stimulated IMLNS PBMC significantly increased 35sulfate GBM uptake (geometric mean, 331 cpm/mg) compared to unstimulated IMLNS PBMC (geometric mean, 200) (p = 0.048).
- Stimulated IMLNS PBMC also showed significantly higher uptake than glomeruli alone stimulated with Con A (geometric mean, 182) (p = 0.008) or glomeruli alone (geometric mean, 146) (p = 0.002).
- No significant differences were observed when glomeruli were cocultured with PBMC from 12 healthy adults.
Conclusions:
- Concanavalin A-stimulated PBMC from IMLNS patients in remission can alter the sulfate metabolism of rat GBM.
- This stimulation mimics the increased 35sulfate uptake seen with PBMC from IMLNS patients in relapse.
- These findings suggest that stimulated PBMC may play a pathogenic role in IMLNS by affecting GBM sulfated compounds and potentially glomerular permeability.