How are immune complexes bound to the primate erythrocyte complement receptor transferred to acceptor phagocytic cells?
How are immune complexes bound to the primate erythrocyte complement receptor transferred to acceptor phagocytic cells?
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DOI：
10.1016/s0161-5890(99)00103-0
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发表时间：
1999-09-01
影响因子：
3.6
通讯作者：
Taylor, RP
中科院分区：
文献类型：
--
作者：
Nardin, A;Lindorfer, MA;Taylor, RP
与灵长类红细胞 (E) 补体受体 (CR1) 结合的免疫复合物 (IC) 从灵长类动物的循环中清除，并定位于肝脏和脾脏中的吞噬细胞，而 E 不会被破坏。 IC 可以通过 C3b 调理作用或使用交联 mAb 复合物（杂聚物，HP）与 E CR1 结合，该复合物包含对 CR1 具有特异性的 mAb 和对抗原具有特异性的 mAb。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。本综述讨论了 E 结合 IC 转移至受体细胞的机制。我们在动物模型中的研究以及我们的体外研究表明，IC 转移是快速的（通常在 10 分钟内 >90%），并且不会导致 E 的裂解或吞噬。使用特定抑制剂的实验以及使用 Fab' 片段制备的 IC 的使用表明，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 的释放与 CR1 的协同丢失相关，随后 IC 被受体细胞摄取和内化。我们认为，Fc 受体对 E 结合 IC 底物的识别和结合允许 E 细胞和受体细胞之间的紧密接触，这反过来又促进 E CR1 的蛋白水解，可能是通过巨噬细胞相关的蛋白酶进行的。蛋白水解后，释放的 IC 被巨噬细胞内化。 (C) 1999 Elsevier Science Ltd. 保留所有权利。
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 CR1 either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain a mAb specific for CR1 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. (C) 1999 Elsevier Science Ltd. All rights reserved.