An Evaluation of the Role of Properdin in Alternative Pathway Activation on Neisseria meningitidis and Neisseria gonorrhoeae
An Evaluation of the Role of Properdin in Alternative Pathway Activation on Neisseria meningitidis and Neisseria gonorrhoeae
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DOI：
10.4049/jimmunol.0903598
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Ram, Sanjay
中科院分区：
文献类型：
--
作者：
Agarwal, Sarika;Ferreira, Viviana P.;Ram, Sanjay
备解素是补体替代途径(AP)的正向调节因子，在抵御侵袭性奈瑟氏菌感染的先天免疫防御中发挥着重要作用。最近，商业上可获得的未分离的备解素被证明能结合到某些生物表面，包括淋球菌，这有助于C3的沉积。除生理的“天然”形式(二聚体、三聚体和四聚体)外，未分馏的备解素还含有聚集体或高阶低聚物。我们在不同的脑膜炎奈瑟氏菌和淋病奈瑟菌株上，使用天然的和普通的备解素，研究了备解素在AP激活中的作用。当用抗备解素单抗阻断备解素功能或从血清中去除备解素时，奈瑟氏菌上的C3沉积显著减少。即使在较高的血清浓度(80%)时，也需要备解素，才能最大限度地促进AP介导的C3在奈瑟雷氏杆菌上的沉积。与先前的观察一致，细菌与未分离的备解素预先孵育，然后添加备解素耗尽的血清，比单独与备解素耗尽的血清孵育时，细菌产生更高的C3沉积。出乎意料的是，在测试的10株NeisSeries菌株中，没有一株与当地的备解素结合。与其无法与奈瑟氏菌结合的情况一致，将细菌与天然备解素预先孵育，然后添加备解素耗尽的血清，并没有引起C3沉积的可检测到的增加。然而，将缺乏备解素的血清与天然备解素A先验地重组后，所有被测试的奈瑟氏菌株上的C3沉积都增加了。总而言之，生理形式的备解素并不直接与脑膜炎奈瑟氏菌或淋病奈瑟菌结合，但通过稳定AP C3转换酶的“传统”机制，在增加AP依赖的C3在细菌上的沉积方面发挥了关键作用。《免疫学杂志》，2010,185：507-516。
Properdin, a positive regulator of the alternative pathway (AP) of complement is important in innate immune defenses against invasive Neisserial infections. Recently, commercially available unfractionated properdin was shown to bind to certain biological surfaces, including Neisseria gonorrhoeae, which facilitated C3 deposition. Unfractionated properdin contains aggregates or high-order oligomers, in addition to its physiological "native" (dimeric, trimeric, and tetrameric) forms. We examined the role of properdin in AP activation on diverse strains of Neisseria meningitidis and N. gonorrhoeae specifically using native versus unfractionated properdin. C3 deposition on Neisseria decreased markedly when properdin function was blocked using an anti-properdin mAb or when properdin was depleted from serum. Maximal AP-mediated C3 deposition on Neisseriae even at high (80%) serum concentrations required properdin. Consistent with prior observations, preincubation of bacteria with unfractionated properdin, followed by the addition of properdin-depleted serum resulted in higher C3 deposition than when bacteria were incubated with properdin-depleted serum alone. Unexpectedly, none of 10 Neisserial strains tested bound native properdin. Consistent with its inability to bind to Neisseriae, preincubating bacteria with native properdin followed by the addition of properdin-depleted serum did not cause detectable increases in C3 deposition. However, reconstituting properdin-depleted serum with native properdin a priori enhanced C3 deposition on all strains of Neisseria tested. In conclusion, the physiological forms of properdin do not bind directly to either N. meningitidis or N. gonorrhoeae but play a crucial role in augmenting AP-dependent C3 deposition on the bacteria through the "conventional" mechanism of stabilizing AP C3 convertases. The Journal of Immunology, 2010, 185: 507-516.