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Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy
A Watanabe1, Y Tomino, K Yokoyama
1Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Abstract:
The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.
Insights
Hydrogen peroxide production by immune cells is elevated in non-insulin dependent diabetes mellitus (NIDDM) patients, especially in advanced stages. This suggests reactive oxygen species may drive diabetic nephropathy progression.
Area of Science:
- Immunology
- Nephrology
- Endocrinology
Background:
- Non-insulin dependent diabetes mellitus (NIDDM) is associated with complications like diabetic nephropathy.
- Polymorphonuclear leukocytes (PMN) are key immune cells involved in inflammation and oxidative stress.
- Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) implicated in tissue damage.
Purpose of the Study:
- To investigate H2O2 production by PMN in NIDDM patients across different disease stages.
- To determine the correlation between H2O2 production and the progression of diabetic nephropathy.
Main Methods:
- Flow cytometry was used to measure H2O2 production by PMN.
- PMN were stimulated with various agents including PMA, FMLP, aggregated human IgG, and Staphylococcus aureus.
- NIDDM patients were categorized into four stages based on microalbuminuria, proteinuria, and renal function.
Main Results:
- PMN H2O2 production was significantly higher in all stages of NIDDM compared to healthy controls.
- Elevated H2O2 production was particularly pronounced in stage IV NIDDM patients (proteinuric with impaired renal function).
- H2O2 production in stage IV NIDDM patients exceeded that in non-diabetic patients with renal impairment.
Conclusions:
- Increased PMN-derived H2O2 production is a feature of NIDDM.
- Elevated ROS may contribute to the pathogenesis and progression of diabetic nephropathy.
- Targeting ROS production could be a therapeutic strategy for diabetic kidney disease.