巨噬细胞移动抑制因子在抗中性粒细胞胞浆抗体相关小血管炎发病机制中的作用

项目名称： 巨噬细胞移动抑制因子在抗中性粒细胞胞浆抗体相关小血管炎发病机制中的作用

项目编号： No.81460145

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郝健

作者单位： 内蒙古医科大学

项目金额： 48万元

中文摘要： 抗中性粒细胞胞浆抗体（ANCA）相关小血管炎（AAV）的发病机制目前未明，ANCA和中性粒细胞起了重要作用，补体C5a与其受体作用是AAV发病的核心环节。巨噬细胞移动抑制因子（MIF）是一种重要的炎症介质和致炎细胞因子，有研究提示MIF在AAV的发病中可能起重要作用。申请者前期研究发现AAV患者血清中MIF的浓度与疾病活动性密切相关，且中性粒细胞经MIF共孵育后，细胞膜表达ANCA靶抗原的水平增加，因此提出如下假设：在AAV的发病机制中，C5a刺激中性粒细胞后，巨噬细胞移动抑制因子可能作为第一信使，以自分泌或旁分泌的方式释放到细胞外，在ANCA的作用下进一步活化中性粒细胞，从而促进C5a致病作用；巨噬细胞移动抑制因子可能与C5a协同参与肾小球内皮细胞的损伤，在AAV的发病机制中发挥致病作用。

中文关键词： 巨噬细胞移动抑制因子；中性粒细胞；抗中性粒细胞胞浆抗体；人肾小球内皮细胞

英文摘要： Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is characterized by pauci-immune necrotizing in?ammation of the small blood vessels. ANCA and neutrophil have been demonstrated to play a central role in the process of AAV. C5a and the neutrophil C5a receptor compose an amplification loop, and is one of the central contributing factors in ANCA-mediated neutrophil recruitment and activation. Later studies have demonstrated macrophage migration inhibitory factor （MIF）is an inflammatory mediator released by macrophages, neutrophils and endothelial cells. MIF is central to the innate immune response system with an upstream role in the inflammatory cascade. Our study has reported circulating MIF levels were elevated in patients with active AAV. According to the previous results, we propose that this scientific hypothesis: MIF triggered by C5a-primed neutrophils acted in an autocrine or paracrine manner, which can further activate neutrophils. MIF may be involved in glomerular endothelial cell injury and the interaction between C5a and MIF could play an important role in the pathogenesis of ANCA associated vasculitis.

英文关键词： macrophage migration inhibitory factor;neutrophil;ANCA;Human Renal Glomerular Endothelial Cells