Leukocyte trafficking in thoracic grafts

 描述(由申请人提供)： 心肌缺血再灌注损伤是器官保存和植入的结果，对心脏移植后的早期和远期预后都有不利影响。由于心力衰竭在退伍军人中非常普遍，这方面的调查具有很高的意义。虽然中性粒细胞是心肌缺血再灌注损伤的关键介质，但在这种形式的无菌炎症过程中，人们对中性粒细胞的运输和激活需求知之甚少。利用我们新开发的小鼠心脏跳动活体成像技术，我们发现了供者心脏中的天然免疫分子在中性粒细胞进入新鲜再灌流心脏移植的移植物组织中所起的作用。这项应用旨在研究心脏移植物心肌缺血再灌注损伤中中性粒细胞募集的机制，并将为开发新的治疗策略提供依据。

 DESCRIPTION (provided by applicant): Myocardial ischemia reperfusion injury, a consequence of organ preservation and implantation, adversely impacts both early and late outcomes after heart transplantation. As heart failure is highly prevalent among the veteran population, this area of investigation is of very high significance. While neutrophils are critical mediators of myocardial ischemia reperfusion injury, little is known about their trafficking and activation requirements during this form of sterile inflammation. Utilizing our newly developed technique of intravital imaging of beating mouse hearts, we have uncovered a role for innate immune molecules in donor hearts for entry of neutrophils into the graft tissue of freshly reperfused cardiac transplants. This application proposes to study mechanisms for neutrophil recruitment during myocardial ischemia reperfusion injury of heart grafts and will allow for the development of new therapeutic strategies.