ABSTRACT
BACKGROUND: Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is efficacious in modulating inflammation and immunity as well as in patients with human immunodeficiency virus infection. This study examined the effect and mechanism of CCR5 blockade in combination with cyclosporine in prolonging cardiac allograft survival in mice. METHODS: Hearts from BALB/c mice were transplanted into C57BL/10 recipients. They were administrated with anti-CCR5 antibody (Ab) or control Ab and cyclosporine or phosphate-buffered (PBS) saline, respectively. To investigate the role of regulatory cells, naïve mice (secondary recipients) underwent adoptive transfer of splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients and cardiac allograft transplantation. RESULTS: Compared with recipients treated with control Ab plus PBS, allografts treated with anti-CCR5 Ab and cyclosporine showed significantly prolonged survival (p < 0.001), markedly decreased CD4+ and CD8+ T cells (p < 0.005), and increased frequency of CD4+CD25+Foxp3+ regulatory cells (23.98% +/- 1.55% vs 6.30% +/- 0.57%, p < 0.005). Adoptive transfer of CD4+CD25+ splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients induced significantly prolonged survival in secondary recipients (p < 0.01 vs adoptive transfer from naïve mice and recipients depleted of CD25+ cells). CONCLUSIONS: CCR5 blockade combined with cyclosporine is effective in protecting the cardiac allograft in a robust murine model. This effect is partly mediated by regulatory cell recruitment and control of effector cell infiltration.
Subject(s)
Antibodies, Anti-Idiotypic/pharmacology , CCR5 Receptor Antagonists , Cyclosporine/pharmacology , Graft Survival/drug effects , Heart Transplantation/methods , Immunosuppressive Agents/pharmacology , Animals , CD4 Antigens/metabolism , Drug Therapy, Combination , Forkhead Transcription Factors/metabolism , Heart Transplantation/pathology , Interleukin-2 Receptor alpha Subunit/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Receptors, CCR5/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology , Transplantation, HomologousABSTRACT
BACKGROUND: Polypyrrole (PPy) has been widely applied in biomedical fields due to its special electronic property. Past 20 years, there are an increasing number of studies on the application of PPy as a potentially electrically addressable tissue/cell support substrate for tissue/cell regeneration.OBJECTIVE: To overall review the application of PPy in tissue engineering field, and to provide a new approach for the research and development of medical biomaterials.METHODS: Pubmed and Chinese biomedicine literature database were searched using key word of "polypyrrole" for documents published between 1990 and 2010. Literatures related to application of PPy in tissue engineering field were included, and the repetitive articles were excluded.RESULTS AND CONCLUSION: Totally 762 papers were searched by computer, according to the inclusive and exclusive criteria, 51 literature were reviewed. Currently, PPy has been widely used in the fields of cardiovascular tissue engineering, bone and muscle tissue engineering, as well as skin tissue engineering. Application of PPy and PPy-based biomaterials hold great potential in development of novel biomedical materials applied in tissue engineering due to their versatile functionality and superior biocompatibility.
