Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis
Open Access
- 4 August 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 78 (4), 862-870
- https://doi.org/10.1189/jlb.1004583
Abstract
Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O2−)‐generating reduced nicotinamide adenine dinucleotide phosphate‐oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA1c) between 7.0% and 8.0%] or poor (HbA1c >8.0%) glycemic control released significantly more O2− than neutrophils from diabetic patients with good glycemic control (HbA1c N‐formyl‐Met‐Leu‐Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble‐ and membrane‐bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47‐phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA1c levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47‐phox and O2− release.Keywords
Funding Information
- National Institutes of Health (PO1 DE13499, PO1 DE13191, R21 DE14478, RR00533, DE14066, DK50015, AI23323)
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