Functional Characterization of a Ficolin-mediated Complement Pathway in Amphioxus
Functional Characterization of a Ficolin-mediated Complement Pathway in Amphioxus
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文昌鱼 Ficolin 介导的补体途径的功能表征
DOI：
10.1074/jbc.m111.245944
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发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Xu, Anlong
中科院分区：
文献类型：
--
作者：
Huang, Huiqing;Huang, Shengfeng;Xu, Anlong
纤维胶凝蛋白介导的补体途径在脊椎动物免疫中起着重要作用，但目前尚不清楚该途径是否存在于无脊椎动物中。在这里，我们确定了同源纤维胶凝蛋白通路组件的头索动物文昌鱼，并调查他们是否已增选到一个功能性纤维胶凝蛋白通路。这些同源物，纤维胶凝蛋白FCN 1，丝氨酸蛋白酶MASP 1和MASP 3，补体成分C3，在粘膜组织和性腺中高度表达，并显着上调细菌感染后。重组FCN 1可以诱导血凝，区分糖组分，并特异性地识别和聚集几种细菌（特别是革兰氏阳性菌株），而不显示杀菌活性。这表明FCN 1是一种专门的模式识别受体。重组丝氨酸蛋白酶MASP 1/3与重组FCN 1形成复合物，促进文昌鱼体液中天然C3蛋白的活化，其中C3作为免疫效应子。我们的结论是文昌鱼已经开发了一个功能性的ficolin补体途径。由于纤维胶凝蛋白途径组分尚未在非脊索动物中报道，我们的研究结果支持了这一观点，即该途径可能代表了补体系统进化中的脊索动物特异性创新。
The ficolin-mediated complement pathway plays an important role in vertebrate immunity, but it is not clear whether this pathway exists in invertebrates. Here we identified homologs of ficolin pathway components from the cephalochordate amphioxus and investigated whether they had been co-opted into a functional ficolin pathway. Four of these homologs, ficolin FCN1, serine protease MASP1 and MASP3, and complement component C3, were highly expressed in mucosal tissues and gonads, and were significantly up-regulated following bacterial infection. Recombinant FCN1 could induce hemagglutination, discriminate among sugar components, and specifically recognize and aggregate several bacteria (especially Gram-positive strains) without showing bactericidal activity. This suggested that FCN1 is a dedicated pattern-recognition receptor. Recombinant serine protease MASP1/3 formed complexes with recombinant FCN1 and facilitated the activation of native C3 protein in amphioxus humoral fluid, in which C3 acted as an immune effector. We conclude that amphioxus have developed a functional ficolin-complement pathway. Because ficolin pathway components have not been reported in non-chordate species, our findings supported the idea that this pathway may represent a chordate-specific innovation in the evolution of the complement system.