Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin
Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin
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DOI：
10.1073/pnas.0402180101
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发表时间：
2004-07-06
影响因子：
11.1
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Matsushita, M;Matsushita, A;Fujita, T
天然免疫中的凝集素补体途径与获得性免疫中的经典补体途径在结构和功能上密切相关。这两种途径都是由胶原蛋白和甘露糖结合凝集素（MBL）相关丝氨酸蛋白酶（MASP）/C1 r/C1 s家族的丝氨酸蛋白酶组成的复合物启动的。据推测，经典途径出现在凝集素途径之后，并且后者的活化机制是部分保守的。经典途径和凝集素途径可以分别追溯到至少软骨鱼和海鞘（urochor-data）。为了阐明补体系统的演变，我们分离和表征了GlcNAc结合凝集素从七鳃鳗（无颌），最原始的脊椎动物，缺乏经典的途径的血清。七鳃鳗GlcNAc结合凝集素是由24-kDa亚基组成的寡聚体。cDNA和系统发育分析表明，七鳃鳗GlcNAc结合凝集素是一个直系同源的哺乳动物C1 q，胶原亚组分的第一个组件参与结合免疫球蛋白的经典途径。七鳃鳗C1 q与MASP-A共纯化，MASP-A是MASP/C1 r/C1 s家族的丝氨酸蛋白酶，其对七鳃鳗C3表现出蛋白水解活性。表面等离子体共振分析表明，七鳃鳗C1 q特异性结合到GlcNAc，但不是各种其他碳水化合物测试。这些结果表明，C1 q可能已经出现作为凝集素，并可能作为初始识别分子的补体系统在先天免疫建立之前，如免疫球蛋白在软骨鱼。
The lectin complement pathway in innate immunity is closely related to the classical complement pathway in adaptive immunity, with respect to the structures and functions of their components. Both pathways are initiated by complexes consisting of collagenous proteins and serine proteases of the mannose-binding lectin (MBL)-associated serine protease (MASP)/C1r/C1s family. It has been speculated that the classical pathway emerged after the lectin pathway, and that the activation mechanism of the latter was partially conserved. The classical and lectin pathways can be traced back to at least cartilaginous fish and ascidian (urochor-data), respectively. To elucidate the evolution of the complement system, we isolated and characterized a GlcNAc-binding lectin from sera of lamprey (agnathans), the most primitive vertebrate that lacks the classical pathway. Lamprey GlcNAc-binding lectin was an oligomer consisting of 24-kDa subunits. cDNA and phylogenetic analyses revealed that the lamprey GlcNAc-binding lectin is an orthologue of mammalian C1q, a collagenous subcomponent of the first component involved in binding to immunoglobulins in the classical pathway. Lamprey C1q copurified with MASP-A, a serine protease of the MASP/C1r/C1s family, which exhibited proteolytic activity against lamprey C3. Surface plasmon resonance analysis showed that lamprey C1q specifically bound to GlcNAc, but not various other carbohydrates tested. These results suggest that C1q may have emerged as a lectin and may have functioned as an initial recognition molecule of the complement system in innate immunity before the establishment of adaptive immunity such as immunoglobulins in the cartilaginous fish.