Selectin blockade plus therapy with low-dose sirolimus and cyclosporin A prevent brain death-induced renal allograft dysfunction
Selectin blockade plus therapy with low-dose sirolimus and cyclosporin A prevent brain death-induced renal allograft dysfunction
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DOI：
10.1111/j.1600-6143.2005.00763.x
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发表时间：
2005-04-01
影响因子：
8.8
通讯作者：
Tilney, NL
中科院分区：
文献类型：
--
作者：
Gasser, M;Waaga-Gasser, AM;Tilney, NL
抗原依赖性和非依赖性因素均影响移植器官的长期功能和存活。脑死亡（BD）是一种重要的抗原非依赖性、供体相关性损伤，可上调外周器官中多种炎症介质。对这种损伤的最早反应之一是移植组织的内皮细胞表达选择素;这些反过来又引发一系列非特异性事件，增强宿主同种异体反应，并且可能因长期免疫抑制的毒性作用而恶化。使用大鼠模型，其中供体BD加重随后的肾移植损伤，我们已经测试了单独使用重组P-选择素糖蛋白配体（rPSGL-Ig）或与西罗莫司（SRL）和环孢素A联合治疗的效果。我们发现，与标准剂量的SRL或环孢素的作用相反，rPSGL-Ig在移植后早期减少炎症，因此较低剂量的维持免疫抑制足以维持长期移植功能。
Both antigen-dependent and -independent factors influence long-term organ allograft function and survival. Brain death (BD), a significant antigen-independent, donor-related injury upregulates a variety of inflammatory mediators in peripheral organs. One of the earliest responses to such an insult is the expression of selectins by endothelial cells of the transplanted tissues; these in turn trigger a cascade of nonspecific events, that enhance host alloresponses and which may be worsened by toxic effects of long-term immunosuppression. Using a rat model in which donor BD accentuates subsequent renal allograft injury, we have tested the effects of therapy with recombinant P-selectin glycoprotein ligand (rPSGL-Ig) alone, or in combination with sirolimus (SRL) and cyclosporin A. We found that in contrast to the effects of standard doses of SRL or cyclosporine, rPSGL-Ig decreased inflammation in the early posttransplant period such that lower doses of maintenance immunosuppression were sufficient to maintain long-term graft function.