Department of Immunology, Genetics and Pathology, Rudbeck Laboratory C5:3, Uppsala University, Sweden.
Immunobiology. 2012 Nov;217(11):1106-10. doi: 10.1016/j.imbio.2012.07.008.
The tick-over theory was first introduced in the 1970s to explain the presence of the initial C3b molecules, which are able to trigger complement activation by the alternative pathway in human plasma under physiological conditions. After the identification of the thioester, the predominant hypothesis has been that this bond is hydrolyzed at a slow but constant rate by nucleophilic attack by H(2)O, leading to the generation of C3(H(2)O). Here we put forward the hypothesis that the rate of hydrolysis of C3 to C3(H(2)O) may be greatly accelerated by the interaction between C3 and a number of biological and artificial interfaces, including gas bubbles, biomaterial surfaces and different lipid surfaces and complexes. We therefore propose that C3 should preferentially be regarded as a contact activated protein rather than a target for passive, random hydrolysis in the fluid phase.
迟滞理论最初于 20 世纪 70 年代被引入，用以解释初始 C3b 分子的存在。在生理条件下，初始 C3b 分子能够通过人血浆中的替代途径触发补体激活。硫酯确定后，主要假说认为，该键通过 H(2)O 的亲核攻击以缓慢但恒定的速率水解，导致 C3(H(2)O)的生成。在这里，我们提出假设，C3 与许多生物和人工界面（包括气泡、生物材料表面和不同的脂质表面和复合物）之间的相互作用可能大大加速 C3 水解为 C3(H(2)O)的速率。因此，我们提出 C3 应该优先被视为接触激活蛋白，而不是在液相中被动、随机水解的靶标。
