Molecular basis of complement activation by ficolins throu the lectin pathsay

纤维胶蛋白通过凝集素途径激活补体的分子基础

基本信息

批准号：
12470079
负责人：
FUJITA Teizo
金额：
$ 8.96万
依托单位：
Fukushima Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470079/
关键词：
Ficolin Lectin Host defeuse complement Lectin pathway Gene targeting MASP 分子進化自然免疫遺伝子改変マウス

项目摘要

Discrimination between self and non-self by lectins is a strategy of innate immunity that is found in both vertebrates and invertebrates. In vertebrates, immune recognition is mediated by ficolins as well as mannose-binding lectin (MBL). Ficolins are the proteins characterized by the presence of an N-terminal collagen-like domain and a C-terminal fibrinogen-like domain, and have been identified in mammalians such as pig, mouse and human. In this project, human L-and H-ficolins were found to form complexes with MASPs, Cis-like serine proteases and sMAP, a truncated form of MASP-2. Upon recognition of carbohydrate patterns on invading microorganisms by these ficolins, the associated MASPs were activated to cleave the complements C3/C4 through the lectin complement pathway. L-ficolin recognized lipteicholic acid and 1,3-β-D glucan, components in the cell wall of microorganisms, as well as N-acetylglucosamine residue on glycoproteins. To further clarify the physiological roles of ficolins and MASPs/sMAP we established ficolin A-deficient and Maspi-deficient mice using gene targeting technique. The phenotype of ficolin A-dificient mice is now under investigation. Masp-1 deficient mice were more susceptible for infection by influenza virus. Sera from Masp 1-deficient mice showed low activation of Masp-2 from the proenzyme form, followed by a delay of complement activation. To explore primitive system of the lectin pathway, ficolins and the other components of the lectin pathway were isolated from lower animals such as ascidian Halocynthia rorezti, our closest invertebrate relatives. The system was suggested to be simply consisted of three components, recognition molecules (ficolin-like and MBL-like lectins), MASP and complement C3. These results suggest that ficolins have a pivotal role as recognition molecules for host defense in all species which emerged after ascidians.

在脊椎动物和无脊椎动物中，自我和非自我歧视是一种免疫力。 C末端纤维蛋白原样结构域在该项目中。通过这些纤维蛋白，将相关的masps激活，通过凝集素补体裂解C3/C4。 SMAP我们建立了ficolin a缺陷型和Maspi缺陷的靶向技术。 -2通过补体激活的延迟，探索凝集素途径的原始系统。结果表明，纤维蛋白具有关键作用，作为在海沿岸出现的所有物种中宿主防御的识别分子。