Lymphatic endothelium as a new immunomodulatory target in lung transplantation

淋巴内皮和同种异体移植排斥反应。肺移植是终末期肺病患者唯一的治疗选择。成功的移植可以提高患者的存活率和生活质量。然而，限制因素是肺移植的慢性排斥反应。30%的受者出现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主要局限于免疫抑制治疗，主要是在t细胞水平上，这与高发病率（如肾衰竭、感染和恶性肿瘤）有关。常规的免疫抑制不能避免慢性排斥反应。一种可能的替代方法可能是靶向淋巴内皮，它参与排斥过程的初始步骤。这一策略已经成功地应用于实验性心脏移植。本项目的目的是1)分析淋巴内皮在移植小鼠肺中的作用，2)研究药物选择（如阻断VEGF-3）来影响淋巴内皮，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.