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Oxidative metabolism of polymorphonuclear leukocytes (PMN) in patients with IgA nephropathy
H C Chen1, Y Tomino, Y Yaguchi
1Department of Medicine, Juntendo University, School of Medicine, Tokyo, Japan.
Abstract:
The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation and the infiltration of PMN in glomeruli were determined in 20 patients with primary IgA nephropathy. The H2O2 production of PMN after the stimulation was measured with a spectrophotometer using horseradish peroxidase as substrate. The results were as follows: 1) when PMN were pretreated with cytochalasin B, H2O2 production after stimulation with heat-aggregated IgG (IgG) or serum-treated zymosan (STZ) was significantly higher in patients with IgA nephropathy than in controls, and 2) there was an increased amount of PMN localized in glomeruli in patients with IgA nephropathy using immunofluorescence of monoclonal anti-PMN antibody. It appeared that the increased renal infiltration of PMN which have a high potential for production of reactive oxygen species might induce the glomerular injuries in patients with IgA nephropathy.
Insights
Patients with IgA nephropathy show increased production of hydrogen peroxide (H2O2) by polymorphonuclear leukocytes (PMN). These immune cells also infiltrate glomeruli, potentially causing kidney damage.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- IgA nephropathy is a primary glomerular disease.
- Polymorphonuclear leukocytes (PMN) play a role in inflammatory processes.
- Reactive oxygen species, like hydrogen peroxide (H2O2), are implicated in tissue damage.
Purpose of the Study:
- To investigate hydrogen peroxide (H2O2) production by PMN in IgA nephropathy patients.
- To assess the infiltration of PMN in the glomeruli of these patients.
- To explore the potential role of PMN-derived reactive oxygen species in glomerular injury.
Main Methods:
- Quantified H2O2 production by PMN using spectrophotometry with horseradish peroxidase.
- Stimulated PMN with cytochalasin B, heat-aggregated IgG, and serum-treated zymosan.
- Assessed glomerular PMN infiltration using immunofluorescence with a monoclonal anti-PMN antibody.
Main Results:
- PMN from IgA nephropathy patients exhibited significantly higher H2O2 production compared to controls after stimulation.
- Increased numbers of PMN were observed within the glomeruli of IgA nephropathy patients.
- A correlation between PMN infiltration and H2O2 production was suggested.
Conclusions:
- Elevated PMN activity and infiltration in IgA nephropathy patients contribute to increased reactive oxygen species production.
- These findings suggest that PMN-mediated oxidative stress may be a key factor in glomerular injury in IgA nephropathy.
- Targeting PMN function could be a potential therapeutic strategy for IgA nephropathy.