gms | German Medical Science

132. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

28.04. - 01.05.2015, München

Role of Lipocalin-2 in a murine kidney transplantation model of allograft rejection

Meeting Abstract

  • Felix Aigner - Klinik für Allgemein-, Visceral- u. Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
  • Muhammad Ashraf - Univ.-Klinik f. Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Innsbruck, Österreich
  • Herbert Maier - Univ.-Klinik f. Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Innsbruck, Österreich
  • Robert Öllinger - Klinik für Allgemein-, Visceral- u. Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland
  • Hubert Schwelberger - Univ.-Klinik f. Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Innsbruck, Österreich
  • Katja Kotsch - Univ.-Klinik f. Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Innsbruck, Österreich
  • Heinz Regele - Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
  • Johann Pratschke - Klinik für Allgemein-, Visceral- u. Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland

Deutsche Gesellschaft für Chirurgie. 132. Kongress der Deutschen Gesellschaft für Chirurgie. München, 28.04.-01.05.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgch635

doi: 10.3205/15dgch635, urn:nbn:de:0183-15dgch6353

Published: April 24, 2015

© 2015 Aigner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Introduction: Organ transplantation is invariably linked to the development of ischemia/reperfusion injury (IRI) which is known to negatively influence allograft function in terms of allograft rejection. Lipocalin-2 (Lcn2/NGAL), rapidly produced by injured nephron epithelia, is one of the most promising new markers of renal damage and delayed graft function. Discrepancy exists about the role of Lcn2 in ameliorating or deteriorating IRI in the graft. Determination of Lcn2 function during IRI and acute allograft rejection could provide new therapeutic options for both application of recombinant Lcn2 and blockade of Lcn2.

Material and methods: Murine kidney transplantation was employed to understand the role of Lcn2 in renal IRI and allograft rejection. In syngenic settings male inbred C57Bl/6 wild-type (wt) and Lcn2-/- mice were used, whereas in allogenic settings BALB/c kidney allografts were transplanted into C57Bl/6 (wt and Lcn2-/-) recipients. Tissue sections were stained with HE and periodic acid-Schiff stain and evaluated according to the updated Banff classification. To estimate kidney function serum creatinine and urea were measured and serum NGAL concentrations were determined by ELISA. Expression of Lcn2 mRNA, cytokines and immune cell surface markers in the renal graft was measured by real time qPCR and immunohistochemical analysis.

Results: Three hours of ischemia followed by 24 hours of reperfusion resulted in a substantial upregulation of Lcn2 as well as in a severe damage to the renal graft, resulting in reduced kidney function. At post transplant day seven histomorphology showed moderate to severe tubulitis, interstitial infiltrate and periarterial lymphocytic aggregates, associated with a significant increase in serum creatinine and urea level. Lcn2, TNF-α, IFN-γ, IL6, IL1-β, ICAM-1 and CD3 were strongly upregulated in the rejecting allografts as compared to the sham operated controls. Lcn2 treatment of the recipient perioperatively resulted in functional and morphologically amelioration of the allograft, though not significantly different between C57Bl/6 wt and Lcn2-/- recepients. Daily immunosuppression with cyclosporine A could prevent histomorphologically proven severe acute allograft rejection.

Conclusion: Lcn-2 could be a potential therapeutic target for the treatment of IRI and acute allograft rejection in a murine kidney transplantation model.