THE ROLE OF COMPLEMENT IN XENOTRANSPLANTATION

总的目标是阐明补体在 异种移植排斥反应的发病机制。 已充分证实 补体激活在超急性异种移植排斥反应中起关键作用 认为猪异种移植物的损伤机制 灵长类动物是由天然抗体和经典补体介导的 通路 超急性排斥反应后存活的异种移植物可能被破坏 几天后发生急性血管排斥反应。 的 急性血管性排斥反应组织学与超急性排斥反应组织学相同 排斥反应，我们假设眼镜蛇毒因子不能补充 CVF激活的成分少量地进入移植物。 这 该项目使用新的补体抑制和失活，以防止 补体与移植物内皮的结合，研究补体对移植物内皮细胞的影响。 结合在内皮细胞活化，并检查结合 免疫活性材料以这样的方式抑制移植物 或延迟急性血管排斥反应。 这些实验代表了 使用更广泛的补体治疗急性血管性排斥反应 抑制掺入激活和抑制补体的试剂。 第二个目的是阐明抗体和 补体与移植物结合引发移植物排斥。 的影响 补体蛋白与内皮细胞单层的结合和生成 将检查补体激活产物。 细胞因子产生 将进行监测，以探索补体结合和内皮 细胞激活进行。 最后，住宿的过程将是 考察 移植物与抗体和补体的相互作用 某些情况下似乎可以保护移植物免受进一步的损伤， 几个实验模型。 这种影响的机制将是 特别强调补体的结合 降解碎片到关键嫁接的位置， 其它活性补体产物的结合被抑制。

The overall objective is to elucidate the role of complement in the pathogenesis of xenograft rejection. It is well established that complement activation plays a key role in hyperacute xenograft rejection and its believed that the mechanism of damage of pig xenograft in primates is mediated by natural antibody and the classical complement pathway. Xenografts that survive hyperacute rejection may be destroyed some days later by a process termed acute vascular rejection. The histology of acute vascular rejection is identical to that of hyperacute rejection and we hypothesize that cobra venom factor does not complement components activated by the CVF in small amounts to the graft. This project uses novel complement inhibition and inactivation to prevent complement binding to graft endothelium, studies the effect of complement binding in endothelial cell activation, and examines the binding of immunologically active materials to the graft in such a way as to inhibit or delay acute vascular rejection. These experiments represent an approach to acute vascular rejection using more extensive complement inhibition incorporating agents which activate and inhibit complement. The second aim is to elucidate the mechanism by which antibody and complement binding to grafts initiate graft rejection. The effect of binding of complement proteins to endothelial monolayers and generation of complement activation products will be examined. Cytokine production will be monitored as to explore how complement binding and endothelial cell activation proceed. Finally, the process of accommodation will be examined. The interaction of grafts with antibody and complement under some circumstances appears to protect graft from further damage in several experimental models. The mechanism of this effect will be explored with particular emphasis on the binding of complement degradation fragments to critical graft sits in such a way that the binding of further active complement products is inhibited.