Functional characterization of the mouse lectin ficolin-B

小鼠凝集素 ficolin-B 的功能表征

基本信息

批准号：
67089915
负责人：
Professorin Dr. Daniela N. Männel
金额：
--
依托单位：
Institut für Immunologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2011-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/67089915?language=en
关键词：
Functional characterization mouse lectin ficolin

项目摘要

Ficolins are members of the collectin family of proteins which in humans and mice are able to recognize pathogen associated molecular patterns (PAMPs) on microbial surfaces. Ficolins trigger the activation of the innate immune system by initiating the complement cascade in serum upon binding to their specific PAMPs. We recently published the first observation on mouse ficolin-B synthesis and showed that, surprisingly, the protein is localized intracellularly in macrophages. In parallel, others have shown that ficolin-B does not associate to serine proteases and, therefore, is unable to activate complement. The relevance of these findings and the mechanism of action of mouse ficolin-B upon bacterial challenge remain to be elucidated. Our preliminary data indicate that ficolin-B expression is up-regulated during activation but down-regulated during maturation of macrophages and bone marrow-derived dendritic cells suggesting a critical role of ficolin-B during early stages of cell activation upon pathogen encounter. In addition, binding assays reveal that some strains of Staph. aureus and Streptococcus pneumoniae are targets of ficolin-B. In this project we propose to study the regulation of ficolin-B expression in immune cells, the identification of its molecular target structure, and its role in cell activation. In this way, we attempt to characterize the ficolin-B-mediated innate immune response and test our hypothesis that ficolin-B plays a role in the immune response.

Ficolins 是蛋白质集合素家族的成员，在人类和小鼠中，该蛋白质能够识别微生物表面上的病原体相关分子模式 (PAMP)。 Ficolins 在与其特定的 PAMP 结合后启动血清中的补体级联反应，从而触发先天免疫系统的激活。我们最近发表了关于小鼠 ficolin-B 合成的第一个观察结果，令人惊讶的是，该蛋白质位于巨噬细胞的细胞内。与此同时，其他人也表明 ficolin-B 不与丝氨酸蛋白酶结合，因此无法激活补体。这些发现的相关性以及小鼠 ficolin-B 对细菌攻击的作用机制仍有待阐明。我们的初步数据表明，ficolin-B 的表达在巨噬细胞和骨髓源性树突状细胞的激活过程中上调，但在成熟过程中下调，这表明 ficolin-B 在遇到病原体时细胞激活的早期阶段发挥着关键作用。此外，结合测定表明一些葡萄球菌菌株。金黄色葡萄球菌和肺炎链球菌是 ficolin-B 的靶标。在本项目中，我们拟研究免疫细胞中 ficolin-B 表达的调节、其分子靶结构的鉴定及其在细胞激活中的作用。通过这种方式，我们试图表征 ficolin-B 介导的先天免疫反应，并检验我们的假设，即 ficolin-B 在免疫反应中发挥作用。