Lymphatic endothelium as a new immunomodulatory target in lung transplantation

淋巴管内皮与同种异体移植排斥反应。肺移植是终末期肺病患者的唯一治疗选择。成功的移植可以提高这些患者的生存率和生活质量。然而，限制因素是肺移植物的慢性排斥反应。30%的受体发生闭塞性细支气管炎综合征，这是慢性排斥反应的临床表现。肺移植受者的死亡主要是由于排斥反应。目前避免排斥反应的策略仅限于主要在T细胞水平上的免疫抑制治疗，这与高发病率（例如肾衰竭、感染和恶性肿瘤）相关。常规免疫抑制不能避免慢性排斥反应。一种可能的替代方案可能是靶向淋巴管内皮细胞，其参与排斥过程的初始步骤。这种策略已经成功地用于实验性心脏移植。该项目的目的是1）分析淋巴管内皮在移植小鼠肺中的作用，2）研究影响淋巴管内皮的药理学选择（例如阻断VEGF-3），从而防止实验性小鼠肺移植中的排斥反应。

Lymphatic endothelium and allograft rejection. Lung transplantation is the only therapeutical option for patients with end-stage lung disease. A successful transplantation improves survival and the quality of life of these patients. The limiting factor, however, is chronic rejection of the lung allograft. 30% of recipients develop bronchiolitis obliterans syndrome which is the clinical manifestation of chronic rejection. Mortality of lung transplant recipients is mainly atrributable to rejection. Current strategies to avoid rejection are limited to immunosuppressive therapy mostly on the T-cell level which is associated with a high morbidity (e.g. renal failure, infection and malignancies). Chronic rejection cannot be avoided with conventional immunosuppression. A possible alternative may be targeting the lymphatic endothelium which is involved in the initial steps of the rejection process. This strategy has already been used successfully in experimental heart transplantation. The aim of this project is 1) to analyze the role of the lymphatic endothelium in transplanted mouse lungs and 2) to study pharmacological options (e.g. blocking VEGF-3) to influence the lymphatic endothelium and thereby prevent rejection in experimental mouse lung transplantation.