Open Access

Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model

Authors: Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

Source: Cell Medicine, Volume 3, Numbers 1-3, January 2012 , pp. 63-74(12)

Publisher: Cognizant Communication Corporation

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Abstract:

The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of novel immunomodulatory strategies for organ transplantation.

Keywords: Allograft; GFP; HLA-B27; Regulatory T cell; Tolerance; Transgenic rat

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/215517912X639379

Publication date: January 1, 2012

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  • The importance of translating original, peer-reviewed research and review articles on the subject of cell therapy and its application to human diseases to society has led to the formation of the journal Cell Medicine. To ensure high-quality contributions from all areas of transplantation, the same rigorous peer review will be applied to articles published in Cell Medicine. Articles may deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, and stem cells, among others. Basic clinical studies and immunological research papers may also be featured if they have a translational interest. To provide complete coverage of this revolutionary field, Cell Medicine will report on relevant technological advances and their potential for translational medicine. Cell Medicine will be a purely online Open Access journal. There will therefore be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow your work to be disseminated to a wider audience and also entitle you to a free PDF, as well as prepublication of an unedited version of your manuscript.
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