内皮损伤和过度炎症是弥散性血管内凝血(DIC)的重要病理环节，寻找其中关键分子并实施靶向干预，有望突破DIC治疗瓶颈。研究证实血小板内皮细胞粘附分子-1（PECAM-1）介导的同/异嗜性亲和是内皮-内皮、内皮-炎症细胞间识别粘附的基础，在维持内皮完整及调节炎症方面至关重要；我们前期研究发现PECAM-1KO小鼠更易发生DIC；首次确定PECAM-1结构域D6是其亲和功能调节区，针对D6区抗体可能通过构象改变增强PECAM-1亲和力；因此，创新性提出靶向调控细胞膜PECAM-1亲和功能以纠正内皮与炎症失衡，从而实现对DIC的有效干预。.本项目将通过嵌合体模式动物明确不同细胞来源PECAM-1与DIC的关系；应用ECIS、纳米盘等技术探讨IgD6抗体驱动PECAM-1亲和力改变对DIC内皮屏障修复、抗炎效应的影响及机制，从而揭示PECAM-1及其亲和功能调控在DIC中的作用，为治疗提供新思路。

Endothelial damage and excessive inflammation are pivotal pathological changes to develop disseminated intravascular coagulation (DIC), if a key molecule can be found and targeted in the pathological progress, the treatment of DIC will make effective improvement and breakthrough progress. Studies show that the role of platelet endothelial cell adhesion molecule-1(PECAM-1) on maintaining endothelial integrity and regulating inflammation is particularly critical，because its hemophilic and heterophilic affinity underlies the interactions between endothelial cells with endothelial cells and inflammatory cells. In our previous studies，we confirmed that the PECAM-1 KO mice was more inclined to occur DIC, and we firstly revealed that the affinity of PECAM-1 can be regulated by its structural domain Ig D6; furthermore, its hemophilic affinity can be enhanced by PECAM-1 IgD6 antibody through conformational changes. Therefore, we innovatively proposed that targeted regulation of the affinity of PECAM-1 on the cell surface may restore the imbalance of endothelium and inflammation, thus effectively interfering with the DIC pathological process. In this project, the aim is to elucidate the relationship between PECAM-1 and DIC through the chimeric animal models；and to explore the effects of antibody-driven affinity modulation of PECAM-1 on endothelial barrier restoration and anti-inflammatory response by the technologies of ECIS, nanodisc, etc. All the above-mentioned is to reveal the function of PECAM-1 and its affinity regulation in DIC, providing novel potential therapeutically approaches for DIC.