ANCA诱导的ROS在调控中性粒细胞凋亡∕NETosis转换中的作用机制

项目名称： ANCA诱导的ROS在调控中性粒细胞凋亡∕NETosis转换中的作用机制

项目编号： No.81200534

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 徐鹏程

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 抗中性粒细胞胞浆抗体（ANCA）是ANCA相关小血管炎（AAV）的标志抗体，可以诱导中性粒细胞产生活性氧（ROS)。NETosis发现于2004年，指中性粒细胞释放出由胞内DNA及各种酶组成的胞外网(NETs），进而发生死亡的现象。NETs对机体具有很强的损伤性，ANCA可以诱导NETs形成。课题组前期研究表明，ANCA是否诱导NETosis依赖于ROS的水平，低水平ROS仅诱导细胞凋亡，高水平ROS则可诱导NETosis。故ROS可能在中性粒细胞从凋亡到NETosis的转换中起关键作用。本研究拟在此基础上采用流式细胞术测定凋亡，利用定量测定DNA检测NETs生成等方法，进一步研究ANCA刺激中性粒细胞时ROS在调控凋亡∕NETosis中的作用及信号通路，明确中性粒细胞凋亡与NETosis之间的关系，并抑制NETosis使细胞向凋亡转化，为从新的角度探究AAV的发病机制及治疗提供理论基础。

中文关键词： 中性粒细胞胞外诱捕网；抗中性粒细胞胞浆抗体；活性氧；C反应蛋白；血栓形成

英文摘要： Neutrophil has a pivatol role in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis(AAV). ANCA can induce the generation of reactive oxygen species (ROS)of neutrophil, which is thought to be the key point of the pathogenitis of AAV. In 2004, a novel type of neutrophil death, neutrophil extracellular trap(NET) cell death, which is also named NETosis, was reported. Upon activation, neutrophils release NETs and then die. NETs are composed of chromatin decorated with granular proteins such as myeloperoxidase, proteinase 3 et al. NETs provide a high local concentration of antimicrobial molecules that kill microbes effectively. NETs are abundant at inflammatory sites, and were shown to be relevant in AAV. ANCA has been reported to be able to induce NETosis. Our previous study has demonstrated that the generation of NETs depended on the level of ROS induced by ANCA. Low-level of ROS could only result in the acceleration of apoptosis of neutrophil, while high-level of ROS could induce the NETosis. So we thought that the ROS should be pivotal to the conversion between apoptosis and NETosis. In the further study, we plan to investigate the role of ROS in the conversion between apoptosis and NETosis further. Apoptosis will be detected with flow cytometry and NETosis will be detected with the measurement of

英文关键词： neutrophil extracellular traps；antineutrophil cytoplasmic antibody；reactive oxygen species；C reactive protein；thrombosis