| There are about2,000,000patients per year with kidney failure. Transplantation hasbeen the most advantageous method in treating kidney failure in final stage for a long time.The development of various preoperative examines and HLA match ensure the success ofkidney transplantation. How to keep the transplant kidney survival functionally for a longterm is always an important problem to solve urgently. There are many factors to influencethe long-term survival of transplant kidney, and which can be divided into nonimmunologicfactors and immunologic factors. Nonimmunologic factors include match consistency, sexand age of donor-recipients. Immunologic factors include whether graft rejection happensor not, the time and intensity of graft rejection. Immunologic factors play a critical role ininfluencing long-term survival of transplant kidney.Cyclosporine A, tacrolimus and rapamycin have been used as conventionalimmunosuppressive agents in clinic to suppress graft rejection through suppressing theactivation and proliferation of T cells. Although the immunosuppressive agents takeconspicuous effect, they also have side effects because of non-selective suppression of Tcells.IL-17is an important proinflammatory cytokine and secreted by CD4+T cells, CD8+Tcells, T cells and neutrophilic granulocytes. It can induce human epidermal cells,endothelial cells and fibroblasts to secrete IL-6, IL-8and G-CSF and promote theexpression of ICAM-1by fibroblasts. It can also recruit neutrophilic granulocytes andpromote vascularization. Previous studies have demonstrated that IL-17plays an importantrole in acute rejection after organ transplantation.The binding of transplantation antigens with antibodies can activate complementsystem in graft rejection. As the key component in complement system, C5can be decomposed into C5a and C5b after activation. C5a is an important mediator ofinflammation and chemotactic factor. It takes biologic effect through binding to C5aR in thesurface of target cells. Although there are many studies about the importance ofcomplement components in graft rejection, the mechanism of C5a in graft rejection is notclear.Objective:To investigate the regulation effect of C5a on the IL-17production during renalallograft rejection.Methods:â‘ The percentage of IL-17+T cells in peripheral blood at indicated time points afterallograft transplantation was measured with flow cytometry (FCM).â‘¡The serum C5a levelat indicated time points was detected after allografttransplantation with enzyme linked immunosorbent assay (ELISA).â‘¢Immunohistochemistry was performed to detect the IL-17expression and C5b-9deposition in normal renal tissues and renal tissues with allograft rejection.â‘£The expression of C5aR on human kindy-2(HK2) and effect of recombinant C5astimulation on IL-17expression in HK2cells was detected with both immunocytochemistryand FCM.Results:â‘ Compared with that of0h, IL-17+T cells percentage was markedly increased inpart of patients at72h after transplantation.â‘¡It was showed that the serum C5a level was significantly higher at1w than that of0h after transplantation.â‘¢Compared with normal kidney tissues, IL-17expression and C5b-9deposition intransplant kidney tissues with acute rejection was obviously increased.â‘£It was found that the expression of C5aR on HK2cellswas constitutive and IL-17expression in HK2cells was obviously increased after stimulation with recombinant C5afor48h. Conclusion:It was suggested that C5a may directly regulate the production of IL-17by binding toC5aR during renal allograft rejection. |
PDF Full Text Request