Hostetter M K, Krueger R A, Schmeling D J
J Infect Dis. 1984 Nov;150(5):653-61. doi: 10.1093/infdis/150.5.653.
In these studies, we have defined the mechanism by which the opsonic fragment of the third component of complement (C3) binds to pathogenic bacteria. With use of purified human C3 to reconstitute the alternative pathway in human serum in which both C3 and C4 had been chemically inactivated, we showed that opsonization of pathogenic serotypes of Streptococcus pneumoniae (serotypes 3, 4, 6A, 14, and 18C) requires the reactive thiolester of native C3. When purified human C3 (thiolester intact) is added to serum deficient in C3 and C4, phagocytic uptake of 3H-labeled pneumococci by polymorphonuclear leukocytes from normal adults is fully reconstituted. However, hydrolysis of the thiolester or reaction of the thiolester with the inhibitor methylamine abolishes opsonization and phagocytosis. Finally, by characterizing those C3 fragments released from pneumococcal surfaces after treatment with 1.0 M hydroxylamine, we have defined a role for covalent-bond formation in the opsonic interaction. Therefore, the presence of the reactive thiolester of C3 is an absolute requirement for the opsonic and covalent binding of the C3b molecule to pathogenic bacteria.
在这些研究中，我们确定了补体第三成分（C3）的调理片段与致病细菌结合的机制。通过使用纯化的人C3在人血清中重建替代途径（其中C3和C4均已被化学灭活），我们发现肺炎链球菌致病血清型（血清型3、4、6A、14和18C）的调理作用需要天然C3的反应性硫酯键。当将纯化的人C3（硫酯键完整）添加到缺乏C3和C4的血清中时，正常成年人多形核白细胞对3H标记肺炎球菌的吞噬摄取得以完全重建。然而，硫酯键的水解或硫酯键与抑制剂甲胺的反应会消除调理作用和吞噬作用。最后，通过表征用1.0 M羟胺处理后从肺炎球菌表面释放的那些C3片段，我们确定了共价键形成在调理相互作用中的作用。因此，C3反应性硫酯键的存在是C3b分子与致病细菌进行调理和共价结合的绝对必要条件。
