Division of Clinical Chemistry, Department of Laboratory Medicine, Lund University, Wallenberg Laboratory, Skåne University Hospital, Malmö, Sweden.
Semin Thromb Hemost. 2011 Jun;37(4):355-61. doi: 10.1055/s-0031-1276584. Epub 2011 Jul 30.
Blood coagulation and complement pathways are two important natural defense systems. The high affinity interaction between the anticoagulant vitamin K-dependent protein S and the complement regulator C4b-binding protein (C4BP) is a direct physical link between the two systems. In human plasma, ~70% of total protein S circulates in complex with C4BP; the remaining is free. The anticoagulant activity of protein S is mainly expressed by the free form, although the protein S-C4BP complex has recently been shown to have some anticoagulant activity. The high affinity binding of protein S to C4BP provides C4BP with the ability to bind to negatively charged phospholipid membranes, which serves the purpose of localizing complement regulatory activity close to the membrane. Even though C4BP does not directly affect the coagulation system, it still influences the regulation of blood coagulation through its interaction with protein S. This is particularly important in states of inherited deficiency of protein S where the tight binding of protein S to C4BP results in a pronounced and selective drop in concentration of free protein S, whereas the concentration of protein S in complex with C4BP remains relatively unchanged. This review summarizes the current knowledge on C4BP with respect to its association with thrombosis and hemostasis.
血液凝固和补体途径是两个重要的天然防御系统。抗凝维生素 K 依赖性蛋白 S 与补体调节剂 C4b 结合蛋白 (C4BP) 之间的高亲和力相互作用是这两个系统之间的直接物理联系。在人血浆中，~70%的总蛋白 S 与 C4BP 形成复合物循环；其余为游离形式。蛋白 S 的抗凝活性主要由游离形式表达，尽管最近已经表明蛋白 S-C4BP 复合物具有一些抗凝活性。蛋白 S 与 C4BP 的高亲和力结合赋予 C4BP 结合带负电荷的磷脂膜的能力，这使得补体调节活性能够在靠近膜的位置定位。尽管 C4BP 不会直接影响凝血系统，但它仍然通过与蛋白 S 的相互作用影响血液凝固的调节。在蛋白 S 遗传性缺乏的情况下，这一点尤为重要，在这种情况下，蛋白 S 与 C4BP 的紧密结合导致游离蛋白 S 的浓度明显且选择性下降，而与 C4BP 结合的蛋白 S 浓度则相对不变。本文综述了 C4BP 的最新研究进展，包括其与血栓形成和止血的关系。
