Kist de Ruijter, L. (Laura) (2014) Complement gemediëerde veranderingen in de geïsoleerde geperdundeerde nier. De IPK als model voor immunologische effecten op de renale orgaanfunctie in transplantatie. thesis, Medicine.
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Abstract
The complement system, as part of the innate immunity, initiates and supports inflammation in the body. Systemic complement activation in brain death causes damage of potential donor kidneys, which affects long-term kidney graft survival. Pathways by which this systemic complement activation injures the kidney are not fully understood yet. Possible routes are induction of local complement production, induction of renal inflammation, direct damage by destructive complement components and hemodynamic changes. This study mimiced a systemic complement activation with ZAS in an isolated perfused kidney model (IPK). Research on renal damage by systemic complement was performed by measuring parameters of organ function, immunohistochemistry, RT-PCR on gene expressions and levels of injury markers in the perfusion medium. Besides that, an ischemia-reperfusion (IR) model was used for determination of the rol of complement in IR. Used model and this study were to limited for outlining the effect of systemic complement activation on local renal complement production and renal inflammation. No clues were found for direct damage by destructive complement components. The IR-model was promising. Hemodynamically, ZAS caused a great reduction in RBF and GFR. Based on existing literature and these results, a hypothesis was formulated for an explanation of this complement mediated renal vasoconstriction independent of mast cells, PMNs and thrombocytes. This hypotheses states an C5a-mediated release of TxA2 by endothelial cells, thereby causing SMCs to contract. A pilot performed in this study on TxA2 release by C5a-stimulated endothelial cells was promising supportive. Formed hypothesis gives new ideas on routes by which complements mediates renal injury in transplantation. Exact determination of this routes contributes to development of therapeutic interventions, which are plausible to improve kidney graft survival.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Seelen, dr. M.A.J. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:54 |
| Last Modified: | 25 Jun 2020 10:54 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1449 |
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