内皮祖细胞（EPC）移植可修复受损肺血管内皮，但受损肺血管的炎症微环境可影响移植EPC的存活。并且，在前期工作中(Cytotherapy, 2009, 11)，我们发现EPC分泌的部分炎症介质可损伤EPC。然而，EPC分泌炎症介质的调控通路，以及炎症介质损伤EPC的作用途径均尚未清楚。在预实验中，我们观察到CD40激活上调EPC分泌ICAM和IL-6，后两者可粘附免疫细胞并攻击EPC自身。基于此，我们拟深入探讨CD40通路介导炎症微环境对EPC的损伤及其机制，主要内容包括：① 体外模拟炎症微环境并分析CD40通路的激活与失活对EPC分泌炎症介质的影响，以及后者对EPC的损伤效应；② 分析CD40通路调控EPC分泌炎症介质的关键信号分子；③ 在体分析CD40通路在炎症微环境致移植EPC损伤中的作用。本项目的完成将明确炎症微环境致EPC损伤的调控通路，并为细胞移植治疗的优化提供理论基础。

The damaged pulmonary vascular endothelium was repaired through the transplantation of endothelial progenitor cells (EPC). However, inevitably these cells could be impaired in local inflammatory microenvironments of pulmonary vascular lesions. In addition, it was noticed in our previous work (Cytotherapy, 2009, 11) that some of the factors released by EPC had inflammatory effects, which would have EPC impaired. Both the pathway regulating the release of inflammatory mediators by EPC and the route mediating the impairment of EPC by inflammatory mediators are still unclear. In preliminary study, we observed that the expressions of ICAM and IL-6 in EPC membranes were up-regulated through the activation of CD40, which would induce the adhesion and attack of circulating immune cell against EPC itself. Therefore, we are about to carry out the research concerning CD40 pathway mediating EPC impairment in the inflammatory microenvironments and the relative mechanisms to the effects. The contents of this project mainly consist of the following sections. First, in the inflammatory microenvironments imitated in vitro, we are going to investigate the influence of the activation and inactivation of CD40 pathway on the secretion of inflammatory mediators by EPC, and the damage effects of these inflammatory mediators on EPC. And then, key downstream signaling molecules are going to be explored in CD40 pathway, which regulates the secretion of inflammatory mediators by EPC. Lastly, we are going to analyze the role of CD40 pathway in the progression of transplanted EPC impairment caused by the inflammatory microenvironments in vivo. It is anticipated that the pathway mediating EPC impairment in the inflammatory microenvironments will be found, and the theory basis of optimizing cell transplantation will be richened if this research is accomplished.