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Production of superoxide anion by polymorphonuclear leukocytes from diabetic patients with or without diabetic
A M Abu el-Asrar1, R T Soliman, S A al-Amro
1Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Abstract:
Oxygen free radicals have been implicated in the pathogenesis of diabetic microangiopathy. The production of superoxide anion (O2-.) by polymorphonuclear leukocytes (PMNs) from 45 insulin-dependent diabetes mellitus patients in the resting state and in response to a soluble stimulus (phorbol myristate acetate) was measured spectrophotometrically and compared with that of 15 age and sex matched controls. The resting superoxide anion production by PMNs from diabetic patients was significantly higher than that of controls (2.17 +/- 1.32 and 1.35 +/- 0.6 nmol/10(5) cells/60 min respectively; p = 0.037). In contrast, PMNs from diabetic patients released significantly lower levels of superoxide anion compared to controls in response to phorbol myristate acetate stimulation (2.33 +/- 2.04 and 3.55 +/- 0.98 nmol/10(5) cells/60 min respectively; p = 0.044). The stimulated superoxide anion production was significantly higher in diabetic patients with retinopathy compared to diabetic patients without retinopathy (2.7 +/- 2.08 and 1.3 +/- 1.6 nmol/10(5) cells/60 min respectively; p = 0.02). Furthermore, stimulated PMNs from diabetic patients with proliferative retinopathy generated superoxide anion at significantly higher rates than did those from diabetics with nonproliferative retinopathy or without retinopathy (3.8 +/- 1.5, 2.08 +/- 2.1 and 1.3 +/- 1.6 nmol/10(5) cells/60 min respectively; p = 0.005). These results suggest that reactive oxygen species produced by PMNs may play a role in the progression of diabetic retinopathy.
Insights
Diabetic patients show higher resting superoxide anion production by polymorphonuclear leukocytes (PMNs). However, stimulated PMNs from diabetics produce less superoxide, with higher production linked to retinopathy severity, suggesting a role in diabetic microangiopathy progression.
Area of Science:
- Biochemistry
- Immunology
- Diabetology
Background:
- Diabetic microangiopathy pathogenesis involves oxygen free radicals.
- Polymorphonuclear leukocytes (PMNs) are key immune cells implicated in inflammatory processes.
- Superoxide anion (O2-.) is a significant reactive oxygen species.
Purpose of the Study:
- To investigate superoxide anion production by PMNs in patients with insulin-dependent diabetes mellitus.
- To compare resting and stimulated superoxide production in diabetic patients versus controls.
- To explore the correlation between superoxide production and diabetic retinopathy progression.
Main Methods:
- Spectrophotometric measurement of superoxide anion production by PMNs.
- Comparison of PMNs from 45 diabetic patients and 15 age/sex-matched controls.
- Assessment of PMN response to phorbol myristate acetate stimulation.
Main Results:
- Resting PMNs from diabetic patients exhibited significantly higher superoxide production than controls (p=0.037).
- Stimulated PMNs from diabetic patients showed significantly lower superoxide production compared to controls (p=0.044).
- Diabetic patients with retinopathy had higher stimulated superoxide production than those without (p=0.02).
- Proliferative retinopathy was associated with the highest stimulated superoxide anion generation (p=0.005).
Conclusions:
- PMN-derived reactive oxygen species may contribute to diabetic microangiopathy.
- Altered superoxide production by PMNs in diabetes could be linked to disease progression.
- The severity of diabetic retinopathy correlates with increased stimulated superoxide anion production.