Nilsson B, Larsson R, Hong J, Elgue G, Ekdahl K N, Sahu A, Lambris J D
Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
Blood. 1998 Sep 1;92(5):1661-7.
Recently, a C3-binding cyclic synthetic peptide (Compstatin) has been identified that binds to complement component C3 and inhibits complement activation. Here we have examined the influence of Compstatin on complement activation and its indirect effects on cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a result of the inhibition of complement activation, the activation of polymorphonuclear leukocytes (PMNs; as assessed by the expression of CD11b) and the binding of these cells (CD16(+)) to the polymer surface were almost completely lost. In contrast, blood cell counts were not affected. Using surface plasmon resonance technology, we have confirmed that Compstatin exerts its inhibitory effect on complement activation by binding to native C3. These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the addition of Compstatin. The properties of Compstatin make Compstatin a promising drug for use in extracorporeal circuits to avoid bioincompatibility reactions, eg, during cardiopulmonary bypass, but also a favorable precursor peptide for the development of an anticomplement drug for oral use.
最近，已鉴定出一种与补体成分C3结合并抑制补体激活的C3结合环合成肽（补体抑制素）。在此，我们在两种体外循环模型中研究了补体抑制素对补体激活的影响及其对全血中细胞反应的间接作用。补体抑制素有效抑制了C3a和sC5b-9的生成以及C3/C3片段与聚合物表面的结合。由于补体激活受到抑制，多形核白细胞（PMN；通过CD11b的表达评估）的激活以及这些细胞（CD16(+)）与聚合物表面的结合几乎完全消失。相比之下，血细胞计数未受影响。使用表面等离子体共振技术，我们证实补体抑制素通过与天然C3结合发挥其对补体激活的抑制作用。这些数据表明，补体抑制素的添加可消除导致PMN激活并使其与生物材料表面结合的补体激活。补体抑制素的特性使其成为用于体外循环以避免生物不相容反应（例如在体外循环期间）的有前景的药物，也是开发口服抗补体药物的良好前体肽。
