CD47和Band3介导的衰老红细胞吞噬机制的单分子定位成像研究

项目名称： CD47和Band3介导的衰老红细胞吞噬机制的单分子定位成像研究

项目编号： No.81501432

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王锋

作者单位： 吉林大学

项目金额： 18万元

中文摘要： 红细胞衰老一直是医学免疫学的研究热点。正常红细胞中发挥抑制吞噬功能的膜蛋白CD47，在衰老红细胞中可能起着促进吞噬的作用。红细胞衰老过程中，Band3蛋白断裂、簇集，形成衰老抗原，通过补体途径促进吞噬。人红细胞表面CD47/Band3呈蛋白复合体形式存在，老鼠红细胞中二者关系尚不明确。细胞衰老时，CD47和Band3如何协调二者的吞噬信号尚有待深入研究。申请人利用dSTORM成像发现：同年轻的老鼠红细胞相比，CD47在衰老的红细胞表面呈簇状分布。此时，CD47/SIRPα传递的吞噬抑制性信号消失。本课题以年轻/衰老的人/鼠红细胞为材料，通过dSTORM成像分析CD47/Band3的空间组装变化，同时检测二者下游的磷酸化信号，从而揭示CD47/Band3空间组装和信号途径转换之间的关系，为阐明衰老红细胞的清除机制提供线索，进而为有核细胞的衰老及红细胞衰老相关疾病的研究提供参考。

中文关键词： 红细胞；衰老；CD47；Band；3；单分子定位显微成像

英文摘要： Red blood cells (RBCs) aging has always been a research focus in medical immunology. As a “marker of self”, CD47 function as a phagocytic inhibitory signal on normal cell, but a phagocytic promoting signal on senescent RBCs. During RBCs senescence, Band3 breaks down, generates senescent cell antigen, and initiates complement C3 fragments mediated phagocytosis. CD47 and Band3 form a macro-complex on human RBCs, while their relationship on mouse RBCs is still not known. During RBCs senescence, the coordination between Band 3 and CD47, and their related phagocytosis signal pathway convertion, still needs further investigation. Our preliminary work found that, comparing with young mRBCs, CD47 formed bigger clusters on aging mRBCs and phagocytic inhibitory signals eliminated. In this study, we will explore the spatial organization of CD47/Band3 at nano-scale using direct stochastic optical reconstruction microscopy. By dissecting the spatial organization of CD47/Band3 on young/aging human/mouse RBCs and their related phagocytosis signal pathway, our work will elucidate the phagocytic mechanism of aging RBCs, and provide new prospects in understanding of nucleated cells aging and related diseases.

英文关键词： Red blood cells;aging;CD47; Band 3; single molecule localization microscopy