CD147对类风湿关节炎中性粒细胞功能的影响及其机制

项目名称： CD147对类风湿关节炎中性粒细胞功能的影响及其机制

项目编号： No.81202299

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 王聪华

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 类风湿关节炎（RA）是由多种炎细胞和细胞因子参与发病，可致残、致死的常见疾病；但是以T、B细胞占主导的传统理论尚不能完全解释RA发病机制。而有效抑制中性粒细胞聚集及RA滑膜细胞的增殖侵袭正逐渐成为RA研究的热点和发展趋势。本项目组在前期发现CD147在RA外周血及滑液中性粒细胞高表达并影响其功能的基础上，拟：①建立中性粒细胞和RA滑膜细胞共培养模型，观察CD147对中性粒细胞趋化、粘附，共培养后MMPs分泌及侵袭等功能的影响；②借助RNAi手段研究CD147表达下调对上述功能的影响；③从"钙闪烁"及信号通路等角度阐明CD147发挥功能的内在机制；④构建联合免疫缺陷鼠-人RA移植物嵌合模型（SCID-HuRAg），探讨CD147单抗对中性粒细胞功能的拮抗效果及作用机制。本研究是对既往CD147影响RA中性粒细胞功能研究的进一步深入，有助于阐明RA发病机制，有望为探索RA新型治疗策略开辟思路。

中文关键词： 关节炎；类风湿；中性粒细胞；CD147；

英文摘要： Rheumatoid arthritis (RA) is a disabling, deadly and common autoimmune disease which is a combination of inflammatory cells and cytokines involved, but traditional theory dominated by T, B cells can not completely explain the pathogenesis of RA. With deepening understanding of neutrophils, effectively inhibit neutrophil aggregation, invasion ability and proliferation of RA synovial cells have become a hot research point and development trend. On the basis of our previous research that highly-expressed CD147 on neutrophils of RA peripheral blood and synovial fluid affect their functionality, we propose to: ① Establish co-culture model of neutrophils and RA synovial cells to observe the role of CD147 on neutrophil's chemotaxis, adhesion ability, secretion of MMPs and invasion function before or after co-culture; ② Observe the effect of down-regulation of CD147 to these functions using RNAi method; ③ Clarify the internal mechanism of CD147's function to the neutrophils from "calcium flicker" and signaling pathways; ④ Explore the effect of CD147 monoclonal antibody on neutrophil's function and mechanism of the antagonistic effect through building severe combined immunodeficient mice-human RA grafts (SCID-HuRAg) model. This study go deep into previous research that CD147 affects functions of RA neutrophil, further re

英文关键词： Arthritis；Rheumatoid；Neutrophils；CD147；