C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase

C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase
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DOI:
10.4049/jimmunol.168.11.5786
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发表时间:
2002-06-01
影响因子:
4.4
通讯作者:
Nilsson, B
Nilsson, B
中科院分区:
医学2区
文献类型:
--
作者:
Andersson, J;Ekdahl, KN;Nilsson, B

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血液和生物材料表面之间的接触诱导立即的补体介导的炎症反应。在这些条件下,补体的旁路途径通常在生物材料表面上启动和扩增。蛋白质如C3吸附到聚合物表面诱导蛋白质的构象变化。基于对结合的C3片段特异性的构象新表位在吸附的C3上的表达,我们假设吸附的C3能够结合因子B并形成功能性C3,B B转化酶。使用石英晶体微量天平来监测蛋白质与聚合物表面的结合,我们已经证明可以形成功能性的含C3的替代途径转化酶,特别是在备解素的存在下。这些数据表明,C3的吸附诱导构象变化,将C3转变为能够参与替代转化酶功能的Cab样分子,并且它们提出了生物材料表面上补体活化的新机制。
Contact between blood and a biomaterial surface induces an immediate complement-mediated inflammatory response. Under these conditions, the alternative pathway of complement is often initiated and amplified on the biomaterial surface. Adsorption of a protein such as C3 to a polymer surface induces conformational changes in the protein. Based on the expression on adsorbed C3 of conformational neoepitopes specific for bound C3 fragments, we have hypothesized that adsorbed C3 is able to bind factor B and form a functional C3,Bb convertase. Using a quartz crystal microbalance to monitor binding of proteins to a polymer surface, we have demonstrated that a functional C3-containing alternative pathway convertase can be formed, in particular, in the presence of properdin. These data indicate that adsorption of C3 induces conformational changes that turn C3 into a Cab-like molecule that is able to participate in the functioning of the alternative convertase, and they suggest a new mechanism for complement activation on a biomaterial surface.