Charlton B, Schindhelm K, Smeby L C, Farrell P C
J Lab Clin Med. 1985 Mar;105(3):312-20.
The effect of specific intravascular IgG depletion on IgG catabolism, generation, and intrabody transfer has been studied in rabbits. In contrast to previous studies, the radiolabeled IgG kinetics were analyzed in the non-steady state. A two-pool model was used to determine IgG distribution, catabolism, generation, and intrabody mass transfer after intravenous injection of 125I-IgG. Circulating IgG was then specifically removed by plasma perfusion through a Protein-A Sepharose column in an extracorporeal circuit. Based on the two-pool analysis, IgG catabolic clearance fell after IgG removal (1.0 ml/hr vs. 0.7 ml/hr), and mean generation rate was unchanged. Plasma levels rose 20 hours after IgG removal as a result equally of contributions from intrabody transfer and of generation. Model parameters from plasma 125I decay analysis overestimated plasma 125I levels in the first 24 hours after removal, although predicted endogenous levels corresponded well with experimental results over a 7-day period. Rapid intravenous infusion of a 7% body weight volume of saline solution during IgG removal resulted in 50% greater plasma levels of 125I-IgG 24 hours after removal. This indicated that an increased lymphatic flow had occurred, resulting in increased IgG transfer from the extravascular to the intravascular space. The two-pool model adequately describes circulating IgG levels after specific IgG removal. Catabolic clearance was found to be a function of IgG level, whereas generation does not appear to be similarly dependent. Both the two-pool model and saline infusion procedure may be applied directly to the planning and optimization of plasma exchange therapy regimens in human autoimmune disease.
已在兔子身上研究了特异性血管内IgG耗竭对IgG分解代谢、生成及体内转移的影响。与之前的研究不同，对处于非稳态的放射性标记IgG动力学进行了分析。静脉注射125I-IgG后，采用双池模型来确定IgG分布、分解代谢、生成及体内质量转移。然后通过体外循环中的蛋白A琼脂糖柱进行血浆灌注，特异性去除循环中的IgG。基于双池分析，去除IgG后IgG分解代谢清除率下降（1.0 ml/小时对0.7 ml/小时），平均生成率未变。去除IgG 20小时后血浆水平升高，这是体内转移和生成共同作用的结果。尽管在7天期间预测的内源性水平与实验结果吻合良好，但在去除后最初24小时内，血浆125I衰变分析得到的模型参数高估了血浆125I水平。在去除IgG期间快速静脉输注占体重7%体积的盐溶液，导致去除后24小时血浆中125I-IgG水平升高50%。这表明淋巴流量增加，导致从血管外到血管内空间的IgG转移增加。双池模型能够充分描述特异性去除IgG后的循环IgG水平。发现分解代谢清除率是IgG水平的函数，而生成似乎并非同样依赖于IgG水平。双池模型和盐溶液输注程序均可直接应用于人类自身免疫性疾病血浆置换治疗方案的规划和优化。
