Surgery Nephrology, University Medical Center Groningen, Groningen, The Netherlands Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Am J Transplant. 2011 Apr;11(4):660-9. doi: 10.1111/j.1600-6143.2011.03475.x.
Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered.
两种先天免疫的中心途径，补体和 Toll 样受体（TLRs），在肾移植固有肾损伤的发病机制中起着重要作用。最近的发现表明补体和 TLR 信号通路之间存在密切的串扰。有人提出丝裂原活化蛋白激酶（MAPKs）可能是连接补体和 TLR 通路的关键分子。补体和 TLRs 是肾缺血再灌注损伤（IRI）的重要介质。除了 IRI 之外，补体 C3 还可以在移植前由于供体的脑死亡（BD）而在肾脏中被上调和激活。已经证明供体肾脏中补体的这种局部上调和激活对肾移植的结果有害。TLR4 及其几种主要配体也由供体 BD 上调，与活体供体相比。重要的是，与上述观察结果一致，接受 TLR4 Asp299Gly/Thr399Ile 基因型供体肾脏的肾移植受者受益。本综述重点讨论了补体和 TLRs 在供体 BD 和缺血再灌注期间与肾损伤的关系及其之间的相互作用。考虑了针对肾移植中补体和 TLR 激活的未来策略。
