Cloning and Characterization of Mannose-Binding Lectin from Lamprey (Agnathans)12
Cloning and Characterization of Mannose-Binding Lectin from Lamprey (Agnathans)12
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DOI：
10.4049/jimmunol.176.8.4861
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发表时间：
2006-04
期刊：
影响因子：
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通讯作者：
Momoe Takahashi;D. Iwaki;A. Matsushita;M. Nakata;M. Matsushita;Y. Endo;T. Fujita
中科院分区：
文献类型：
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作者：
Momoe Takahashi;D. Iwaki;A. Matsushita;M. Nakata;M. Matsushita;Y. Endo;T. Fujita
病原体的识别是由一组模式识别分子介导的，这些模式识别分子识别大类微生物所共有的保守的病原体相关分子模式。甘露糖结合凝集素 (MBL) 是一种模式识别分子，通过凝集素途径激活与 MBL 相关丝氨酸蛋白酶 (MASP) 相关的补体。最近，从尾索动物（孤生海鞘）的血浆中分离出一种 MBL 样凝集素。这种海鞘凝集素具有碳水化合物识别结构域，但胶原蛋白样结构域被另一个序列取代。为了阐明 MBL 的起源，本研究的目的是确定最原始脊椎动物七鳃鳗中 MBL 同源物的结构和功能。使用N-乙酰氨基葡萄糖(GlcNAc)-琼脂糖柱，从七鳃鳗血清中分离出MBL样凝集素(p25)并进行cDNA克隆。根据推导的氨基酸序列，该凝集素具有胶原区域和典型的碳水化合物识别结构域。这种凝集素还结合甘露糖、葡萄糖和 GlcNAc，但不结合半乳糖，这表明它在结构和功能上与哺乳动物 MBL 相似。此外，它与七鳃鳗 MASP 相关，并且 MBL-MASP 激活了液相和病原体表面的七鳃鳗 C3。结合系统发育分析，七鳃鳗 MBL 很可能是哺乳动物 MBL 的直系同源物。由于获得性免疫似乎仅从有颌脊椎动物开始建立，因此七鳃鳗中的凝集素补体途径作为先天免疫的主要贡献者之一，在保护身体免受微生物侵害方面发挥着关键作用。
The recognition of pathogens is mediated by a set of pattern recognition molecules that recognize conserved pathogen-associated molecular patterns shared by broad classes of microorganisms. Mannose-binding lectin (MBL) is one of the pattern recognition molecules and activates complement in association with MBL-associated serine protease (MASP) via the lectin pathway. Recently, an MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian. This ascidian lectin has a carbohydrate recognition domain, but the collagen-like domain was replaced by another sequence. To elucidate the origin of MBLs, the aim of this study is to determine the structure and function of the MBL homolog in lamprey, the most primitive vertebrate. Using an N-acetylglucosamine (GlcNAc)-agarose column, MBL-like lectin (p25) was isolated from lamprey serum and cDNA cloning was conducted. From the deduced amino acid sequence this lectin has a collagenous region and a typical carbohydrate recognition domain. This lectin also binds mannose, glucose, and GlcNAc, but not galactose, indicating that it is structurally and functionally similar to the mammalian MBLs. Furthermore, it associated with lamprey MASPs, and the MBL-MASP activated lamprey C3 in fluid-phase and on the surface of pathogens. In conjunction with the phylogenetic analysis, it seems likely that the lamprey MBL is an ortholog of the mammalian MBL. Because acquired immunity seems to have been established only from jawed vertebrates onward, the lectin complement pathway in lamprey, as one of the major contributors to innate immunity, plays a pivotal role in defending the body against microorganisms.