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首页> 外文期刊>American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons >Complement mediated renal inflammation induced by donor brain death: role of renal C5a-C5aR interaction.
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Complement mediated renal inflammation induced by donor brain death: role of renal C5a-C5aR interaction.

机译：供体脑死亡诱导的补体介导的肾脏炎症：肾脏C5a-C5aR相互作用的作用。

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摘要

Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complement contributes to allograft injury remains to be elucidated. The aim of this study was to investigate systemic C5a release after BD in human donors and direct effects of C5a on human renal tissue. C5a levels were measured in plasma from living and brain-dead donors. Renal C5aR gene and protein expression in living and brain-dead donors was investigated in renal pretransplantation biopsies. The direct effect of C5a on human renal tissue was investigated by stimulating human kidney slices with C5a using a newly developed precision-cut method. Elevated C5a levels were found in plasma from brain-dead donors in concert with induced C5aR expression in donor kidney biopsies. Exposure of precision-cut human kidney slices to C5a induced gene expression of pro-inflammatory cytokines IL-1 beta, IL-6 and IL-8. In conclusion, these findings suggest that systemic generation of C5a mediates renal inflammation in brain-dead donor grafts via tubular C5a-C5aR interaction. This study also introduces a novel in vitro technique to analyze renal cells in their biological environment.
机译：与来自活体供体的肾脏相比，从脑死亡的供体中获取的肾脏移植后的同种异体移植功能受损。供体脑死亡（BD）触发炎症反应，包括全身和局部补体激活。全身激活补体促成同种异体移植损伤的机制仍有待阐明。这项研究的目的是调查BD后人类供体的全身性C5a释放以及C5a对人肾组织的直接作用。在活体和脑死亡捐献者的血浆中测量C5a水平。在肾脏移植前活检中研究了活体和脑死亡供体中的肾脏C5aR基因和蛋白质表达。通过使用新开发的精确切割方法用C5a刺激人肾切片来研究C5a对人肾组织的直接作用。发现脑死亡的供者血浆中的C5a水平升高，与供体肾脏活检中诱导的C5aR表达一致。将精确切割的人肾切片暴露于C5a诱导的促炎性细胞因子IL-1 beta，IL-6和IL-8的基因表达。总之，这些发现表明，系统生成的C5a通过肾小管C5a-C5aR相互作用介导了脑死亡供体移植物中的肾脏炎症。这项研究还介绍了一种新的体外技术来分析肾细胞的生物学环境。

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