C5L2 promotes local renal inflammation after donor brain death.

Jager, N.M. (2015) C5L2 promotes local renal inflammation after donor brain death. thesis, Medicine.

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Abstract

Introduction: Renal transplantation is the first choice of treatment in end stage kidney disease. Kidneys for transplantation can be obtained from living, non-heart beating and heart beating (brain death) donors. However, kidneys retrieved from brain-dead donors show inferior results compared to their living counterparts, demonstrated in reduced post-transplant function and survival. Possibly, systemic inflammation induced upon donor brain death affect organ viability prior to organ retrieval. As part of the inflammatory response, the complement system is activated, reflected by elevating levels of the pro-inflammatory anaphylatoxin C5a. The two known receptors for C5a are C5aR and C5L2. In this study, we examine the contribution of C5aR and C5L2 to donor brain death induced renal inflammation. Methods: We will use knock-out mice to look at the specific pathogenesis of brain death induced kidney injury. Brain death will be induced in wildtype, C5aR-/- and C5L2-/- mice. In order to achieve this, we developed a mouse brain death model with a 3 hours stable brain death period. After termination of the mice, blood and organs (kidneys, liver, heart and spleen) will be harvested for analysis. Results: The C5L2-/- mice, but not C5aR-/- mice, show reduced renal gene expression levels of KC, TNFα, MCP-1 and P-selectin upon donor brain death. Discussion: These results implicate that C5L2, instead of C5aR, would be a target for intervention in order to prevent renal allograft priming in brain-dead donors.

Item Type:	Thesis (Thesis)
Supervisor name:	Seelen, Dr. M.A.J.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:51
Last Modified:	25 Jun 2020 10:51
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1190

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