Kennedy D M, Skillen A W, Self C H
Department of Clinical Biochemistry, Medical School, University of Newcastle Upon Tyne, UK.
Clin Exp Immunol. 1993 Dec;94(3):447-51. doi: 10.1111/j.1365-2249.1993.tb08216.x.
As elevated levels of glycated IgG have been detected in the plasma of diabetics we have investigated whether glycation of IgG affects its vascular clearance rate, using a mouse model system. Polyclonal mouse IgG was aseptically incubated for 14-19 days with 0.5 M glucose in 0.1 M phosphate buffer (pH 7.4) at 37 degrees C. As control, IgG was incubated under identical conditions but with no added glucose. After incubation, both forms were labelled with 125I and injected intravenously into BALB/c mice. The rate of vascular clearance of the glycated IgG was found to be significantly higher than the control IgG in the periods 5-24 h (P < 0.001, n = 6) and 24-48 h (P < 0.01, n = 6) after injection. After 2-3 days the mice were killed and the major organs were harvested. With glycated IgG there was a significant increase in the 125I accumulated in the kidney (P < 0.02). In later experiments, dual labelling with 131I and 125I allowed mixtures of glycated and unglycated IgG to be injected into the same mouse so that the vascular clearance of both forms of IgG could be followed simultaneously. These experiments confirmed that glycation of the IgG significantly increases its vascular clearance rate.
由于在糖尿病患者血浆中检测到糖化IgG水平升高，我们使用小鼠模型系统研究了IgG糖基化是否会影响其血管清除率。将多克隆小鼠IgG在37℃下于0.1M磷酸盐缓冲液（pH 7.4）中与0.5M葡萄糖无菌孵育14 - 19天。作为对照，IgG在相同条件下孵育，但不添加葡萄糖。孵育后，两种形式都用125I标记，并静脉注射到BALB/c小鼠体内。发现糖化IgG在注射后5 - 24小时（P < 0.001，n = 6）和24 - 48小时（P < 0.01，n = 6）的血管清除率显著高于对照IgG。2 - 3天后处死小鼠并收获主要器官。对于糖化IgG，肾脏中积累的125I有显著增加（P < 0.02）。在后续实验中，用131I和125I进行双重标记，使得糖化和未糖化IgG的混合物可以注射到同一只小鼠体内，从而能够同时追踪两种形式IgG的血管清除情况。这些实验证实，IgG的糖基化显著提高了其血管清除率。
