Activation of human complement by liposomes: a model for membrane activation of the alternative pathway.
Activation of human complement by liposomes: a model for membrane activation of the alternative pathway.
复制标题
脂质体激活人类补体：替代途径的膜激活模型。
作者：
C. M. Cunningham;M. Kingzette;R. Richards;C. Alving;T. Lint;H. Gewurz
发现脂质体模型膜可以激活人类补体的替代途径。通过与脂质体一起孵育的血清中的C3转化和成分消耗来测量激活。 C3 转化不需要经典途径的 C1 或 C2，因为它在 C1r 缺乏患者的血清、C2 缺乏患者的血清以及含有 EGTA 和 MgCl2 的缓冲液中的正常血清中观察到。脂质体与 C2 缺乏血清的孵育导致组分 C3 至 C9 的消耗，而在替代途径激活的典型特征中没有消耗 C1 或 C4。该反应进一步显示需要旁路途径因子 D，并且不依赖于抗体。替代途径的激活取决于脂质体的膜组成。脂质体需要正电荷才能产生 C3 转化。脂质体胆固醇浓度和磷脂脂酰链长度和不饱和度都会影响激活，表明膜流动性的重要性。含有二肉豆蔻酰磷脂酰胆碱和胆固醇的带正电荷的脂质体需要某些糖脂的存在才能进行 C3 转化。确定膜成分的脂质体对补体旁路的激活可能为研究细胞膜旁路补体途径的激活提供合适的模型。
Liposomal model membranes were found to activate the alternative pathway of human complement. Activation was measured by C3 conversion and component consumption in serum that had been incubated with liposomes. C3 conversion did not require C1 or C2 of the classical pathway, since it was observed in serum from a C1r-deficient patient, serum from a C2-dificient patient, and normal serum in buffer containing EGTA and MgCl2. The incubation of liposomes with C2-deficient serum resulted in consumption of components C3 through C9 with no consumption of C1 or C4 in a profile typical of alternative pathwya activation. The reaction was further shown to require alternative pathway factor D, and to be independent of antibody. Activation of the alterative pathway was dependent on the membrane composition of the liposomes. A positive charge was required for liposomes to produce C3 conversion. Liposomal cholesterol concentration and phospholipid fatty acyl chain length and unsaturation all influenced activation, suggesting the importance of membrane fluidity. Positively charged liposomes containing dimyristoyl phosphatidylcholine and cholesterol required the presence of certain glycolipids for C3 conversion. The activation of the alternative complement pathway by liposomes of defined membrane composition may provide a suitable model for the study of alternative pathway activation by cellular membranes.