Meryhew N L, Shaver C, Messner R P, Runquist O A
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
J Lab Clin Med. 1990 Jun;115(6):719-28.
The mechanisms of immune clearance in normal BALB/c mice were studied by kinetic analysis of the clearance of immunoglobulin-sensitized red blood cells. A rate equation, derived from a model for the clearance of sensitized cells, was used to quantitate four rate constants regulating the individual rate-determining steps in the overall clearance process. A linear relationship was demonstrated between the level of antibody sensitization and constants regulating complement-dependent sequestration (k1), deactivation and release of cells back into the circulation (k2), complement-dependent phagocytosis (k4), and Fc-mediated sequestration and phagocytosis (k3). Clearance rate constants did not change with age in either female or male mice; nor was there a significant difference between the mean values in female versus male mice. The validity of the model was tested by altering serum complement levels to determine whether the predicted changes in complement-dependent rate constants k1, k2, and k4 would occur. Depletion of serum complement by cobra venom factor resulted in a significant decrease in complement-dependent sequestration (k1) and phagocytosis (k4) (p less than 0.001) but had no significant effect on Fc-mediated clearance function (k3). As serum complement was replenished, a greater-than-normal percentage of red blood cells sequestered by the complement clearance pathway underwent phagocytosis (k4) rather than being deactivated and released back into the circulation (k2). Demonstration that the derived rate constants are predictably sensitive to manipulation of a major clearance factor increases the confidence in using this technique and model to study immune clearance in experimental and naturally occurring disease states.
通过对免疫球蛋白致敏红细胞清除的动力学分析，研究了正常BALB/c小鼠的免疫清除机制。从致敏细胞清除模型推导得出的速率方程，用于定量调节整体清除过程中各个速率决定步骤的四个速率常数。抗体致敏水平与调节补体依赖性隔离（k1）、细胞失活并释放回循环（k2）、补体依赖性吞噬作用（k4）以及Fc介导的隔离和吞噬作用（k3）的常数之间呈现线性关系。雌性和雄性小鼠的清除速率常数均不随年龄变化；雌性小鼠与雄性小鼠的平均值之间也无显著差异。通过改变血清补体水平来测试模型的有效性，以确定补体依赖性速率常数k1、k2和k4是否会出现预测的变化。用眼镜蛇毒因子消耗血清补体导致补体依赖性隔离（k1）和吞噬作用（k4）显著降低（p小于0.001），但对Fc介导的清除功能（k3）无显著影响。随着血清补体的补充用眼镜蛇毒因子消耗血清补体导致补体依赖性隔离（k1）和吞噬作用（k4）显著降低（p小于0.001），但对Fc介导的清除功能（k3）无显著影响。随着血清补体的补充，通过补体清除途径隔离的红细胞进行吞噬作用（k4）而非失活并释放回循环（k2）的百分比高于正常水平。所推导的速率常数对主要清除因子的操作具有可预测的敏感性，这一证明增加了使用该技术和模型研究实验性和自然发生疾病状态下免疫清除的信心。
