Role of coagulation and pulmonary xenograft injury

凝血和肺异种移植损伤的作用

• 批准号: 6608785
• 负责人: EDWARD CANTU
• 金额: $ 4.81万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-08 至 2004-07-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6608785
• 关键词: anaphylatoxins; anticoagulants; antigen antibody reaction; baboons; blood coagulation; complement; complement pathway; diphosphonate; genetically modified animals; lung injury; lung transplantation; macrophage; postdoctoral investigator; protein C; swine; transplant rejection; xenotransplantation

DESCRIPTION (provided by applicant): Our purpose is to determine the role of coagulation system activation and inadequate regulation within the pulmonary xenograft on endothelial cell activation, inflammatory augmentation and pulmonary xenograft injury. Initiation of the coagulation system coincides with the acute lung injury that is caused by a) ischemia-reperfusion b) complement activation c) probably antibody binding and d) the pro-coagulant and anti-fibrinolytic actions of pulmonary macrophages. Coagulation system dysregulation allows for uncontrolled acceleration of coagulation with cascading effects on the endothelial cell and the inflammatory system. Strategies to decrease the initiating events leading to activation of the coagulation system are our focus. We plan to 1) deplete the pulmonary macrophages by repetitive administration of intravenous liposomal clodronate to determine their role in initiation of the diffuse intravascular coagulation, endothelial cell activation, and pulmonary xenograft injury 2) determine the importance of xenoreactive antibody binding to Gala1 -3Gal epitopes in pulmonary xenograft injury by depleting antibody in the absence of complement activation using a-gal trisaccharide-PEG conjugates in conjunction with complement inhibition using C1-inhibitor and anti- C5a and 3) inhibit and regulate the coagulation system through the use of inhibition of tissue factor dependent activation of factors IX and X using TFPI or ASIS, and inhibition of factor VIlla and Va by Activated Protein C to assess the effects on endothelial cell function, inflammatory system activation and xenograft function.

描述（由申请人提供）：我们的目的是确定凝血系统激活和肺异种移植物内部细胞激活，炎症增强和肺异种移植损伤的作用。凝血系统的启动与急性肺损伤相吻合，该急性肺损伤是由a）缺血 - 重新灌注b）补体激活c）可能的抗体结合和d）肺巨噬细胞的促凝结和抗凝聚作用。凝血系统失调允许不受控制的凝结加速，对内皮细胞和炎症系统的级联影响。减少导致激活凝血系统的启动事件的策略是我们的重点。我们计划1）通过重复施用静脉内脂质体氯膦酸盐来耗尽肺巨噬细胞，以确定它们在弥漫性弥漫性血管内凝结，内皮细胞的激活和肺内皮移植损伤中的作用2）确定通过与甲状腺肿的结合的重要性 - 在不进行补体激活的情况下，使用A-gal Trisaccharide-PEG结合偶联的抗体与补体抑制剂结合使用C1抑制剂和抗C5A和3）和3）抑制和调节凝结系统，通过使用抑制因素依赖于TFPI或X的因素来调节凝结系统，并通过抑制因子和X抑制因素和X。内皮细胞功能，炎症系统激活和异种移植功能。

项目成果

Economic evaluation of everolimus vs. azathioprine at one year after de novo heart transplantation.

从头心脏移植后一年依维莫司与硫唑嘌呤的经济评估。

• DOI: 10.1111/j.1399-0012.2004.00312.x
• 发表时间: 2005
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Radeva,JasminaI;Reed,ShelbyD;Kalo,Zoltan;Kauf,TeresaL;Cantu3rd,Edward;Cretin,Nathalie;Schulman,KevinA
• 通讯作者: Schulman,KevinA