The Role Of Toll-like Receptors 2 And 4 In Cardiac Allograft Rejection

Objective: To explore the role of Toll-Like Receptors 2 and 4 in Cardiac Allograft Rejection in the model of Wistar to SD rat cardiac allotransplantation .Materials and methods: Donor(Wistar rat) and recipient(SD rat) were divided randomly into two groups. Group A(pretransplant): Before heterotopic heart transplantation of Wistar rats to SD rats , peripheral blood of SD rat was collected, and mononuclear cells, monocytes and lymphocytes were Isolated; Group B(post transplant): Establishing the model of Wistar to SD rat cardiac allotransplantation,peripheral blood of SD rat was collected when left ventricular contraction of Donor heart is stopped ,it was the time of reaching the peak time of transplantation rejection reactions,and mononuclear cells, monocytes and lymphocytes were Isolated. The mRNA level of TLR2,TLR4,MyD88,TRIF6,NF-κB p65 in mononuclear cells were detected by Semi-quantitative RT-PCR and Quantitative real-time RT-PCR. the expression of TNF-α,IFN-γ,IL-2,IL-10in peripheral blood were observed by ELISA. Costimulatory molecules CD80, CD86 on the surface of monocytes and lymphocytes were detected by flow cytometry.Results: (1) The mRNA level of TLR2,TLR4,MyD88,TRIF6,NF-κB p65:the level of Group B was significantly higher than Group A,(p<0.05);(2) The results of TNF-αin the peripheral blood of recipients(pg/ml):the mean value of Group A was 11.06±2.21,Group B was 440.56±37.59, Group B is higher significantly than Group A,P<0.05;(3) The results of IFN-γin the peripheral blood of recipients(pg/ml): the mean value of Group A was 4.52±0.48,Group B was 488.70±22.13, Group B is higher significantly than Group A,P<0.05;(4) The results of IL-2 in the peripheral blood of recipients(pg/ml): the mean value of Group A was 0.77±0.03,Group B was 4.67±0.04, Group B is higher significantly than Group A,P<0.05;(5) The results of IL-10 in the peripheral blood of recipients(pg/ml): the mean value of Group A was 19.97±1.70,Group B was 45.45±1.58, Group B is higher significantly than Group A,P<0.05;(6)The ratio of CD80 on the surface of monocytes(%):the mean value of Group A was 5.08±2.05%, Group B was 33.68±7.57%, Group B is higher significantly than Group A,P<0.05;(7) The ratio of CD86 on the surface of monocytes(%):the mean value of Group A was 7.52±5.73%, Group B was 35.02±5.65%, Group B is higher significantly than Group A,P<0.05;(8) The ratio of CD80 on the surface of lymphocytes (%):the mean value of Group A was 4.46±2.84%, Group B was 34.44±7.22%, Group B is higher significantly than Group A,P<0.05;(9) The ratio of CD86 on the surface of lymphocytes (%):the mean value of Group A was 9.65±6.46%, Group B was 36.80±7.16%, Group B is much higher than Group A,P<0.05;Conclusions: Our results suggest activation of innate immunity in heart-transplant recipients through TLR2 and TLR4 contributes to the development of rejection after cardiac transplantation. The reduced expression of TLR2 and TLR4 may be one of the mechanisms which inhibits the development of cardiac allograft rejection.