Kozel T R, Weinhold L C, Lupan D M
Department of Microbiology and Cell and Molecular Biology Program, University of Nevada, Reno 89557, USA.
Infect Immun. 1996 Aug;64(8):3360-8. doi: 10.1128/iai.64.8.3360-3368.1996.
Candida albicans is a potent activator of the complement system. The objective of this study was to characterize factors that influence the kinetics for activation of C3 and binding of C3 fragments to C. albicans. Factors that were examined included the surface properties of the yeast and contributions of the classical and alternative complement pathways. The results showed that incubation of hydrophobic, hydrophilic, or germinating yeast cells in normal human serum (NHS) containing radiolabeled C3 led to immediate accumulation of C3 on all three cell types, although the rate of accumulation of C3 on germinating cells was lower. An examination of the sites for early C3 binding showed that classical pathway initiation led to immediate, synchronous binding over the entire cell surface. A blockade of the classical pathway by absorption of putative classical pathway initiators or by chelation of calcium limited activation to the alternative pathway. Binding of C3 solely via the alternative pathway was characterized by a significant lag in the initial binding kinetics. In the absence of classical pathway initiation, the early cellular sites for C3 binding appeared as random, asynchronous foci of C3 that appeared to expand with time. The factor(s) mediating rapid deposition of C3 that was characteristic of the classical pathway initiation was reciprocally cross-absorbed by hydrophilic and hydrophobic C. albicans but was not removed by absorption of NHS with Saccharomyces cerevisiae, encapsulated Cryptococcus neoformans, or nonencapsulated C. neoformans. Delayed binding of C3 produced by absorption of serum was largely reversed by addition to the absorbed serum of immunoglobulin G isolated from NHS, indicating a significant role for a naturally occurring anti-C. albicans immunoglobulin C. in classical pathway initiation.
白色念珠菌是补体系统的强效激活剂。本研究的目的是确定影响C3激活动力学以及C3片段与白色念珠菌结合的因素。所研究的因素包括酵母的表面特性以及经典和替代补体途径的作用。结果表明，将疏水、亲水或正在发芽的酵母细胞在含有放射性标记C3的正常人血清（NHS）中孵育，会导致C3在所有三种细胞类型上立即积累，尽管C3在正在发芽细胞上的积累速率较低。对早期C3结合位点的检查表明，经典途径的启动导致在整个细胞表面立即同步结合。通过吸收假定的经典途径启动子或螯合钙来阻断经典途径，可将激活限制在替代途径。仅通过替代途径的C3结合的特征是初始结合动力学存在明显滞后。在没有经典途径启动的情况下，C3早期细胞结合位点表现为随机、异步的C3焦点，且似乎随时间扩展。介导经典途径启动所特有的C3快速沉积的因子可被亲水和疏水白色念珠菌相互交叉吸收，但不能通过用酿酒酵母、有荚膜新生隐球菌或无荚膜新生隐球菌吸收NHS来去除。通过吸收血清产生的C3延迟结合在很大程度上可通过向吸收的血清中添加从NHS分离的免疫球蛋白G来逆转，这表明天然存在的抗白色念珠菌免疫球蛋白C在经典途径启动中起重要作用。
