The essential role of annexin A1 mimetic peptide in the skin allograft survival

Authors

  • Rodrigo Antonio Parra Teixeira,

    1. Post-Graduation in Structural and Functional Biology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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  • Kallyne Kioko Oliveira Mimura,

    1. Post-Graduation in Structural and Functional Biology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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  • Leandro Pires Araujo,

    1. Post-Graduation in Structural and Functional Biology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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  • Karin Vicente Greco,

    1. Department of Surgical Research, Northwick Park Institute for Medical Research – University College London, London, UK
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  • Sonia Maria Oliani

    Corresponding author
    1. Post-Graduation in Structural and Functional Biology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
    2. Department of Biology, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), São Paulo State University (UNESP), São José do Rio Preto, Brazil
    • Correspondence to: Prof. S. M. Oliani, Department of Biology, Instituto de Biociências, Letras e Ciências Exatas; São Paulo State University (UNESP), Rua Cristovão Colombo, 2265, São José do Rio Preto, SP, Brazil, 15054-000. E-mail: smoliani@ibilce.unesp.br

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Abstract

Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection. Studies have demonstrated the anti-inflammatory effects of the annexin A1 (AnxA1) in the regulation of transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograft model was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Mice were used for the skin allograft model and pharmacological treatments were carried out using either the AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3 days before surgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expression of AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26 increased skin allograft survival related with inhibition of neutrophil transmigration and induction of apoptosis, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1 and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, the combination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared with the cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigations in vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphorylation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role in augmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration and enhancement of apoptosis. This effect may lead to the development of new therapeutic approaches relevant to transplant rejection. Copyright © 2013 John Wiley & Sons, Ltd.

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