Artikel
Alzheimer precursor protein (APP) is differentially expressed during acute rejection of rat kidneys
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Veröffentlicht: | 20. Mai 2011 |
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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.