The change in the glycosylation of human leukocytes in immunosuppressive environment
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1
University of Warsaw, Faculty of Biology, Poland
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2
Jagiellonian University, Institute of Zoology, Poland
Cell and organ transplantation has become a mainstay of therapy for end-stage organ failure.The global effect of immunosuppressive drugs on the immune system predisposes a patient to the development of infection,cancer. An effect of immunosuppressive drugs, crucial for the successful transplantation of organs, on glycosylation of immune cells is not known.Glycans decorate the surfaces of all of the key molecules involved in the innate and adaptive immune response. The proper functioning of immune cells in response to alloantygeny, depends on the process of glycosylation of receptor proteins. Changes in the glycosylation profile of T cell receptor may influence the induction of response against the transplant.The aim of this study was to determine the effect of mTOR inhibitor (rapamycin-RAPA) and calcineurin inhibitors (cyclosporin A-CsA and tacrolimus-Tac), used singly and in two-drug combinations, on the glycosylation of mononuclear human cells (MNCs).MNCs were induced in two-way mixed leucocytes reaction (MLR) in the environment of different regimens of immunosuppression. The surface glycosylation of MNCs was identified by flow cytometry using lectins which selectively recognite specific carbohydrate structures. We observed changes in glycosylation of the analysed cells in the presence of mTOR and/or calcineurin inhibitors. Moreover, the environment of two-drug combinations influenced the glycosylation of MLR immune cells. The immunosuppressive drugs decreased the amount of PHAL- and VVL-positive cells, but the lowest percentage of staining cell it was observed in case of CsA and Tac treated cells. The calcineurin inhibitors reduced of PNA-,UEA- and GNA-positive glycans, while mTOR inhibitor enhanced glycans recognized by UEA lectin.
Acknowledgements
Acknowledgements.
This study was supported by grants no. K/ZDS/003253 (Jagiellonian University) and IP2010003370 (University of Warsaw). We thank Lidia Malchar for expert technical assistance
References
[1] BocianK et al. (2010) Nephrol Dial Transplant, 25:710-7.Bocian K,Borysowski J,Wierzbicki P,Wyzgał J,Kłosowska D,Białoszewska A,Pączek L, Gó́rski A, Korczak-Kowalska G. Rapamycin, unlike cyclosporine A, enhances suppressive functions of in vitro-induced CD4+CD25+Tregs.Nephrol Dial Transplant 2010; 25 :710–717
[2] Grigorian A., Mkhikian H., Demetriou M. Interleukin-2, interleukin-7, T cell-mediated autoimmunity,and N-glycosylation. Ann. N.Y. Acad. Sci. 2012, 1253:49-57
[3] Gleeson P. A. The sweet side of immunology : glycobiology of the immune system. Immunol. Cell Biol. 2008, 86:562-563
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Keywords:
leucocytes,
Glycosylation,
allostimulation,
calcineurin inhibitors,
mTOR inhibitors
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Bocian
K,
Pocheć
E,
Dolińska
M and
Korczak-Kowalska
G
(2013). The change in the glycosylation of human leukocytes in immunosuppressive environment.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00618
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Katarzyna Bocian, University of Warsaw, Faculty of Biology, Warsaw, 02-096, Poland, kbocian@biol.uw.edu.pl