title: Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.
abstract: 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.
authors: Surgery Nephrology, University Medical Center Groningen, Groningen, The Netherlands Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. j.damman@chir.umcg.nl
authors: Jeffrey
authors: J
authors: Damman
authors: Mohamed R
authors: MR
authors: Daha
authors: Willem J
authors: WJ
authors: van Son
authors: Henri G
authors: HG
authors: Leuvenink
authors: Rutger J
authors: RJ
authors: Ploeg
authors: Marc A
authors: MA
authors: Seelen
mesh_terms: D000818:Animals; D001926:Brain Death / Q000503:physiopathology*; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016030:Kidney Transplantation / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000209:etiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D051193:Toll-Like Receptors; D003165:Complement System Proteins