非造血细胞上CD47-TSP1信号对血管内皮细胞的调控及在小鼠心脏移植排斥反应中的作用

减轻移植物损伤和排斥是维持移植器官长期存活的关键。申请者已结题项目及前期工作中发现：造血细胞（HTCs）和非造血细胞（Non-HTCs）上表达的CD47具有不同意义，HTCs上表达的CD47可与巨噬细胞和树突状细胞表面的信号调节蛋白α（SIRPα）作用，传递抑制信号，缺乏CD47的HTCs，可激活巨噬细胞和树突状细胞，并被其快速排斥；与之相反，组织细胞等Non-HTCs上CD47缺失，不仅不能通过SIRPα介导巨噬细胞对实体器官移植物的排斥，反而通过某种机制促进了移植物的存活。推测：Non-HTCs上的CD47很可能与其配体凝血酶敏感蛋白1（TSP1）作用，通过对血管内皮细胞的调控，参与了器官移植物排斥反应。本项目将利用小鼠心脏移植模型，研究Non-HTCs上CD47-TSP1信号对血管内皮功能的调控及参与器官移植物排斥的具体机制，阐明CD47-TSP1信号在实体器官移植中的作用及意义。

Reducing graft injury and rejection is the key to maintain long-term survival of transplanted organs. With the previous work of applicant, we found that CD47 expressed on hematopoietic cells (HTCs) and non-hematopoietic cells (Non-HTCs) has different meanings. CD47 which expressed on HTCs can interact with signal regulating protein (SIRPα) which expressed on dendritic cells and macrophages, and transfer suppression signal. HTCs which lack of CD47 will be rapidly rejected by activated dendritic cells and macrophages because of losing CD47- SIRPαsignaling pathway. CD47 which expressed on Non-HTCs, such as tissue cells, can not induce solid organ grafts rejection mediated by SIRPαexpressed on macrophages. On the contrary, CD47 which expressed on Non-HTCs promote the survival of organ grafts by some unknown mechanisms. We presume that CD47 expressed on Non-HTCs may regulate a variety of physiological functions of vascular endothelial cells through its ligand thrombospondin-1(TSP1), and participate in organ grafts rejection. The project will investigate the mechanisms of CD47expressed on Non-HTCs which interacted with TSP1 in vascular endothelial cells regulation, by using mouse heart transplantation model. We want to clarify the mechanisms and significance of CD47-TSP1 signal in solid organ transplantation.