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The essential role of annexin A1 mimetic peptide in the skin allograft survival
Author(s) -
Teixeira Rodrigo Antonio Parra,
Mimura Kallyne Kioko Oliveira,
Araujo Leandro Pires,
Greco Karin Vicente,
Oliani Sonia Maria
Publication year - 2016
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1773
Subject(s) - annexin a1 , annexin , apoptosis , transplantation , pharmacology , medicine , mapk/erk pathway , kinase , cancer research , immunology , chemistry , biology , flow cytometry , microbiology and biotechnology , biochemistry
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.