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Complement profile and activation mechanisms by different LDL apheresis systems

机译:不同LDL血液分离系统的补体谱和激活机制

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Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by means of selective LDL apheresis is indicated in otherwise uncontrolled familial hypercholesterolemia. During blood-biomaterial interaction other constituents than the LDL particles are affected, including the complement system. We set up an ex vivo model in which human whole blood was passed through an LDL apheresis system with one of three different apheresis columns: whole blood adsorption, plasma adsorption and plasma filtration. The concentrations of complement activation products revealed distinctly different patterns of activation and adsorption by the different systems. Evaluated as the final common terminal complement complex (TCC) the whole blood system was inert, in contrast to the plasma systems, which generated substantial and equal amounts of TCC. Initial classical pathway activation was revealed equally for both plasma systems as increases in the C1rs-C1inh complex and C4d. Alternative pathway activation (Bb) was most pronounced for the plasma adsorption system. Although the anaphylatoxins (C3a and C5a) were equally generated by the two plasma separation systems, they were efficiently adsorbed to the plasma adsorption column before the ?outlet?, whereas they were left free in the plasma in the filtration system. Consequently, during blood-biomaterial interaction in LDL apheresis the complement system is modulated in different manners depending on the device composition.
机译:在其他情况下无法控制的家族性高胆固醇血症中,表明通过选择性LDL血液分离术体外清除低密度脂蛋白(LDL)胆固醇。在血液-生物材料相互作用期间,除LDL颗粒外的其他成分也受到影响,包括补体系统。我们建立了一个离体模型,其中人类全血通过LDL血液分离系统通过三个不同的血液分离柱之一:全血吸附,血浆吸附和血浆过滤。补体激活产物的浓度显示出不同系统的激活和吸附模式明显不同。与血浆系统相比,全血系统被认为是最终的通用末端补体复合物(TCC),与血浆系统相比,血浆是惰性的。随着C1rs-C1inh复合体和C4d的增加,两个血浆系统的初始经典途径活化均被揭示。对于血浆吸附系统,替代途径激活(Bb)最为明显。尽管过敏毒素(C3a和C5a)是由两个血浆分离系统平均产生的,但它们在“出口”之前被有效地吸附到了血浆吸附柱上,而在过滤系统中却被游离在血浆中。因此,在LDL血液采血术中的血液与生物材料相互作用期间,补体系统会根据设备的组成以不同的方式进行调节。

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