Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis

Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic com- plications. 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 neutro- phils from diabetic patients with good glycemic con- trol (HbA1c <7.0%) and neutrophils from nondia- betic, healthy individuals upon stimulation with 4- phorbol 12-myristate 13-acetate or 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 phos- phorylation 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 en- hanced 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 phosphor- ylation of p47-phox and O2 - release. J. Leukoc. Biol.