Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation
Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation
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DOI：
10.1182/blood.v92.5.1661
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发表时间：
1998-09-01
期刊：
影响因子：
20.3
通讯作者：
Lambris, JD
中科院分区：
文献类型：
--
作者：
Nilsson, B;Larsson, R;Lambris, JD
最近，已鉴定出一种 C3 结合环状合成肽（Compstatin），它可以与补体成分 C3 结合并抑制补体激活。在这里，我们在两个体外循环模型中研究了坎普他汀对补体激活的影响及其对全血细胞反应的间接影响。坎普他汀有效抑制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丧失。相反，血细胞计数未受影响。利用表面等离子共振技术，我们证实Compstatin通过与天然C3结合而发挥对补体激活的抑制作用。这些数据表明，补体激活导致 PMN 激活并结合到生物材料表面，可以通过添加 Compstatin 来消除。坎普他汀的特性使坎普他汀成为一种有前途的药物，可用于体外循环以避免生物不相容性反应，例如在体外循环期间，而且也是开发口服抗补体药物的有利前体肽。 (C) 1998 年，美国血液学会。
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. (C) 1998 by The American Society of Hematology.