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

• Published in: Journal of leukocyte biology Vol. 78; no. 4; pp. 862 - 870
• Main Authors: Karima, M., Kantarci, A., Ohira, T., Hasturk, H., Jones, V. L., Nam, B‐H., Malabanan, A., Trackman, P. C., Badwey, J. A., Van Dyke, T. E.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.10.2005
• Subjects: diabetes; Diabetes Mellitus - metabolism; Diabetes Mellitus - physiopathology; Diglycerides - metabolism; Female; Humans; Male; Middle Aged; NADPH Oxidases; Neutrophils - metabolism; Periodontitis - complications; Periodontitis - physiopathology; Phosphoproteins - metabolism; Phosphorylation; Protein Kinase C - metabolism; signal transduction; Superoxides - metabolism; Time Factors
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.1004583

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 <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4β‐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 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.