De Toni S, Piva E, Lapolla A, Fontana G, Fedele D, Plebani M
Department of Laboratory Medicine, University of Padua, Italy.
Ann N Y Acad Sci. 1997 Dec 15;832:363-7. doi: 10.1111/j.1749-6632.1997.tb46264.x.
Periodontal disease, a frequent complication of diabetes mellitus, is the major cause of tooth loss. However, studies on neutrophil function in patients with this condition have yielded contradictory findings. The NADPH oxidase activity of 40 diabetic patients with periodontosis who were on metabolic control was evaluated and compared with that in 40 healthy subjects. Superoxide anion production was measured by a photometric method, with NBT reduction at 490 nm in a microplate reader and by a microscopic method, with a percentage of positive PMNs with granules of formazan in the cytoplasm. When the PMN respiratory burst was activated by phorbol myristate acetate (PMA), a protein kinase C (PKC) soluble activator, superoxide production of diabetics (4.31 +/- 1.67 A x 10(-3)/min) and normal subjects (4.25 +/- 1.25 A x 10(-3)/min) was comparable by photometric method, whereas a significantly defective response to opsonized zymosan was observed when the microscopic method was used (58 +/- 17% in diabetics and 66 +/- 18% in controls; p = 0.05). Therefore in patients with diabetes the impact on PMN function is of multifactorial origin, and is probably correlated to the glucose level and to glycation of PMN protein, such as NADPH oxidase or myeloperoxidase. Alternatively, glucose in PMN may be reduced by aldose reductase to polyols, and this pathway requires NADPH, the coenzyme for the respiratory burst. Moreover, we found that superoxide production in response to opsonized zymosan was reduced in diabetic patients. The activation of protein tyrosine kinase (PTK) is an important mechanism underlying transmembrane signaling and, moreover, protein tyrosine phosphorylations, stimulated by zymosan receptor-mediated activation, might be caused by the activation of specific PTK, whereas activation by PMA is probably mediated through another PKC type.
牙周病是糖尿病常见的并发症，也是牙齿缺失的主要原因。然而，关于这种疾病患者中性粒细胞功能的研究结果相互矛盾。对40名代谢得到控制的糖尿病牙周病患者的NADPH氧化酶活性进行了评估，并与40名健康受试者的进行比较。通过光度法，在酶标仪中于490nm处测量NBT还原情况来测定超氧阴离子的产生，同时通过显微镜法，计算细胞质中有甲臜颗粒的阳性PMN的百分比。当用佛波醇肉豆蔻酸酯乙酸酯（PMA，一种蛋白激酶C（PKC）可溶性激活剂）激活PMN呼吸爆发时，通过光度法测得糖尿病患者（4.31±1.67 A×10⁻³/分钟）和正常受试者（4.25±1.25 A×10⁻³/分钟）的超氧产生相当，而当使用显微镜法时，观察到对调理酵母聚糖的反应明显缺陷（糖尿病患者为58±17%，对照组为66±18%；p = 0.05）。因此，在糖尿病患者中，对PMN功能的影响是多因素的，可能与血糖水平以及PMN蛋白（如NADPH氧化酶或髓过氧化物酶）的糖基化有关。或者，PMN中的葡萄糖可能被醛糖还原酶还原为多元醇，而该途径需要呼吸爆发的辅酶NADPH。此外，我们发现糖尿病患者对调理酵母聚糖的超氧产生减少。蛋白酪氨酸激酶（PTK）的激活是跨膜信号传导的重要机制，此外，酵母聚糖受体介导的激活所刺激的蛋白酪氨酸磷酸化可能由特定PTK的激活引起，而PMA的激活可能通过另一种PKC类型介导。
