gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Alzheimer precursor protein (APP) is differentially expressed during acute rejection of rat kidneys

Meeting Abstract

  • Andreas Hecker - Universitätsklinikum Gießen, Klinik für Allgemein-, Viszeral-, Thorax-, Transplantationschirurgie, Gießen
  • Sigrid Wilker - Universitätsklinikum Gießen, Klinik für Allgemein-, Viszeral-, Thorax-, Transplantationschirurgie, Gießen
  • Srebrena Atanasova - Universitätsklinikum Gießen, Klinik für Allgemein-, Viszeral-, Thorax-, Transplantationschirurgie, Gießen
  • Jörg Wilhelm - Universitätsklinikum Gießen, Institut für Pathologie, Gießen
  • Winfried Padberg - Universitätsklinikum Gießen, Klinik für Allgemein-, Viszeral-, Thorax-, Transplantationschirurgie, Gießen
  • Veronika Grau - Universitätsklinikum Gießen, Klinik für Allgemein-, Viszeral-, Thorax-, Transplantationschirurgie, Gießen

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch713

DOI: 10.3205/11dgch713, URN: urn:nbn:de:0183-11dgch7130

Published: May 20, 2011

© 2011 Hecker et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: We investigate leukocytes which accumulate in blood vessels of rat renal allografts during acute rejection. These leukocytes are remarkably rich in monocytes (70%) and display pro- and anti-inflammatory properties during fatal and reversible acute rejection, respectively. Allograft blood monocytes are potentially involved in the destruction of renal transplants and in triggering chronic allograft vasculopathy.

Materials and methods: Isogeneic and allogeneic renal transplantation was performed in Lewis rats, Dark Agouti (DA) and Fischer 344 (F344) rats served as allograft donors. DA kidneys are destroyed by acute rejection within 5 days post-transplantation, whereas F344 grafts undergo reversible acute rejection peaking on day 9 and develop chronic rejection in the long run.

Results: Genome-wide transcriptional profiling surprisingly suggested that the mRNA-expression of Alzheimer precursor protein (APP) by intravascular graft leukocytes is increased during reversible acute rejection of F344-kidneys. This result was corroborated by real-time RT-PCR. APP-over-expression was even more pronounced during fatal rejection of DA-kidneys. Immunohistochemistry with antibodies to APP detected immunopositive material in allograft monocytes double-stained with monoclonal antibody ED1 (CD68-like antigen). In contrast, Westernblotting with antibodies to the C-terminal region of APP revealed no changes in the expression of the native APP (100 kDa). A second immunoreactive protein with an apparent molecular mass of about 50 kDa was abundantly detected in isograft leukocytes but neither in DA nor in F344 allografts. This fragment has been described by others to be associated with APP processing.

Conclusion: We suggest that APP is involved in acute renal allograft rejection. Although the biological function of APP is unknown, numerous therapeutic strategies have been developed targeting APP and its cleavage products to treat Alzheimer´s disease. This enables us to kill two birds with one stone: a better understanding of APP function and the development of novel therapies preventing acute and chronic organ rejection.