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Published on: January 23, 2018
Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes
W Lee Hand1, Debra L Hand, Yvonne Vasquez
1Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA. lee.hand@ttuhsc.edu
Abstract:
The predisposition to infection and chronic inflammation in diabetes may in part be related to the effects of hyperglycemia or other metabolic abnormality on polymorphonuclear leukocytes (PMN). We evaluated oxidative respiratory burst activity (superoxide production) in non-stimulated and stimulated PMN from 70 stable type 2 Hispanic diabetic patients, as compared to 70 healthy Hispanic individuals without diabetes. The influences of protein kinase C (PKC) inhibitors and certain antibiotics on superoxide production were examined. Both resting and stimulated (PMA, zymosan) PMN from diabetic individuals produced more superoxide than PMN from controls. Inhibitors of PKC, a possible mediator of the augmented respiratory burst activity, decreased superoxide production in all (resting and stimulated) diabetic and control PMN. Azithromycin, which is markedly concentrated by PMN, profoundly inhibited superoxide generation in all groups of diabetic and control cells. PMN from Hispanic diabetic patients produced greater quantities of superoxide than non-diabetic controls. This increased oxidative respiratory burst activity may predispose to infection and chronic inflammation in diabetes. PKC inhibitors and azithromycin inhibited this respiratory burst response. The possible role of PKC (especially PKC beta) as the mediator of this augmented respiratory burst response requires further evaluation, and may lead to therapeutic studies with appropriate inhibitors.
Insights
Type 2 diabetes patients exhibit heightened superoxide production in polymorphonuclear leukocytes (PMN), potentially increasing infection risk. Protein kinase C inhibitors and azithromycin reduced this oxidative burst activity in diabetic and control subjects.
Area of Science:
- Immunology
- Metabolic Disorders
Background:
- Diabetes mellitus is associated with increased susceptibility to infections and chronic inflammation.
- Hyperglycemia and metabolic abnormalities in diabetes may impact immune cell function, specifically polymorphonuclear leukocytes (PMN).
Purpose of the Study:
- To evaluate oxidative respiratory burst activity (superoxide production) in PMN from type 2 diabetic patients compared to healthy controls.
- To examine the effects of protein kinase C (PKC) inhibitors and azithromycin on PMN superoxide production.
Main Methods:
- Assessed superoxide production in non-stimulated and stimulated (PMA, zymosan) PMN from 70 type 2 Hispanic diabetic patients and 70 healthy Hispanic controls.
- Investigated the impact of PKC inhibitors and azithromycin on superoxide generation.
Main Results:
- PMN from diabetic individuals showed significantly higher superoxide production at rest and upon stimulation compared to controls.
- PKC inhibitors reduced superoxide production in PMN from both diabetic and control groups.
- Azithromycin markedly inhibited superoxide generation in all tested PMN.
Conclusions:
- Increased oxidative respiratory burst activity in PMN may contribute to infection and inflammation in type 2 diabetes.
- PKC and azithromycin demonstrate potential as modulators of this heightened PMN response, warranting further investigation for therapeutic applications.
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