Nardin A, Lindorfer M A, Taylor R P
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville 22908, USA.
Mol Immunol. 1999 Sep-Oct;36(13-14):827-35. doi: 10.1016/s0161-5890(99)00103-0.
Immune complexes (IC) bound to the primate erythrocyte (E) complement receptor (CR1) are cleared from the circulation of primates and localized to phagocytic cells in the liver and spleen without E destruction. IC can be bound to E CRI either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain a mAb specific for CRI and a mAb specific for an antigen. The long-term goal of our work is to apply the HP system to the treatment of human diseases associated with blood-borne pathogens. This review discusses the mechanism by which the E-bound IC are transferred to acceptor cells. Our studies in animal models as well as our in vitro investigations indicate that IC transfer is rapid (usually >90% in 10 min) and does not lead to lysis or phagocytosis of the E. Experiments with specific inhibitors and the use of IC prepared with Fab' fragments suggest that transfer depends mainly upon recognition by Fc receptors on the acceptor cell. Moreover, we find that IC release from the E is associated with a concerted loss of CR1, and is followed by uptake and internalization of the IC by the acceptor cell. We suggest that recognition and binding of the E-bound IC substrates by Fc receptors allows close contact between the E and acceptor cells, which in turn facilitates proteolysis of E CR1, presumably by a macrophage-associated protease. After proteolysis, the released IC are internalized by the macrophages.
与灵长类红细胞（E）补体受体（CR1）结合的免疫复合物（IC）可从灵长类动物的循环系统中清除，并定位于肝脏和脾脏中的吞噬细胞，而不会导致E被破坏。IC可以通过C3b调理作用或与交联的单克隆抗体复合物（异聚物，HP）结合到E CRI上，其中HP包含对CRI特异的单克隆抗体和对抗原特异的单克隆抗体。我们工作的长期目标是将HP系统应用于治疗与血源性病原体相关的人类疾病。这篇综述讨论了与E结合的IC转移至受体细胞的机制。我们在动物模型中的研究以及体外研究表明，IC转移迅速（通常在10分钟内>90%），且不会导致E的裂解或吞噬。使用特异性抑制剂的实验以及用Fab'片段制备的IC的实验表明，转移主要取决于受体细胞上Fc受体的识别。此外，我们发现IC从E上释放与CR1的协同丢失有关，随后IC被受体细胞摄取并内化。我们认为，Fc受体对与E结合的IC底物的识别和结合使E与受体细胞紧密接触，这反过来又促进了E CR1的蛋白水解，推测是由巨噬细胞相关蛋白酶介导的。蛋白水解后，释放的IC被巨噬细胞内化。
