Vrij, E. (Edwin) de (2012) Complement C5b-9 deposition is not linked to accumulating platelets in acute or chronic renal transplant rejection. thesis, Medicine.
Full text available on request.Abstract
Background: Early injury of the renal graft, for example after brain death or ischemia-reperfusion, increases the incidence of acute rejection with increased morbidity, and increases the risk of chronic transplant dysfunction and long term graft loss. Identifying pathogenic mechanisms leading to graft injury might reveal new targets for intervention to improve graft survival. Recent evidence shows that activation of the complement and coagulation systems are involved in mediating transplant-related injury. Interestingly, a growing body of evidence suggests interaction between both systems. Specifically platelets and complement are intertwined. Platelets can activate the complement system, whereas complement can activate platelets. In this study, we investigated the amount and localization of platelets and complement C5b-9 in human and rat renal allografts subjected to different damaging events before or after transplantation (i.e., brain death, ischemia-reperfusion injury, acute rejection, and chronic transplant dysfunction). Methods: Cryo sections of kidneys from rat models (BD, IRI, acute rejection, CTD) and of corresponding human kidney biopsies (ATN, Banff Ia, Ib, IIa, IIb, chronic rejection) were analyzed for the platelet marker CD61 and complement activation marker C5b-9 by immunohistochemistry. The amount and localisation of the stainings were analyzed. Results: Platelet deposition was increased in glomeruli of rat kidneys with acute rejection, and more peritubular platelet aggregates were found in human acute renal rejection Banff Ia biopsies. Complement C5b-9 was found on the basal side of cortical tubuli in both rat and human kidneys suffering from chronic transplant dysfunction or chronic rejection respectively. The extent of C5b-9 staining encircling the tubulus was higher in rat kidneys with chronic transplant dysfunction. No colocalization could be demonstrated between platelets and complement C5b-9. Conclusion: This study shows increased deposition of platelets and platelet aggregates in acute renal rejection, and C5b-9 in chronic transplant dysfunction and chronic rejection of the kidney. No apparent colocalization could be found between platelets and complement C5b-9.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Lisman, Prof. dr. Ton 1 and Seelen, Dr. Marc 2 and Damman, Dr. Jeffrey 1 and University Medical Center Groningen and Department of Surgery1 and Department of Nephrology2 |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:02 |
| Last Modified: | 25 Jun 2020 11:02 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2224 |
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