Effect of immature dendritic cells derived from bone marrow on rejection of orthotopic liver transplantation in rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Immature dendritic cells have strong antigen uptake and processing ability, but the lack of a variety of costimulatory molecules cannot activate and proliferate initial T cells to produce immune response, which can lead to T cell anergy, thus inducing low immune response or antigen immune specific tolerance. Simultaneously, immature dendritic cells can induce hyporeactivity of allogeneic antigen-specific T cells, thus prolonging the survival time of transplanted organs. OBJECTIVE: To investigate the effect of immature dendritic cells on liver rejection after orthotopic liver transplantation in rats and its mechanism. METHODS: According to the weight of DA and Lewis rats, the rats were randomly divided into three groups, and the liver transplantation model of DA-Lewis rats was established by “two-cuff” method. The rats of control group received no measures. The rats of cyclosporine group were treated with 10 mg/kg cyclosporine from the second day after operation, once a day, for 7 days. The rats of the immature dendritic cell group were injected with 1×106 immature dendritic cells from bone marrow of DA rats one day before operation through dorsal penile vein; the injection was repeated twice with an interval of 10 minutes. The livers of all these rats were removed 7 days after operation. Hematoxylin-eosin staining was used to observe the pathological changes. The mRNA and protein expressions of SHIP, AKT, IKK and IKβ in these three groups were detected by qRT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) Compared with the control group, the survival time of cyclosporine group and immature dendritic cell group was significantly longer (P < 0.05). (2) In cyclosporine group and immature dendritic cell group, the number of infiltrating mononuclear cells and lymphocytes in the portal area of liver tissue was less, the structure of hepatic lobule was not significantly damaged, and the inflammatory cells in hepatic artery, portal vein and bile duct were significantly less than those in control group, which did not reach the level of severe acute rejection. (3) Compared with the control group, the mRNA expression of IKβ in the cyclosporine group and immature dendritic cell group was increased, while the mRNA expression of SHIP, AKT and IKK significantly decreased (P < 0.05). (4) Compared with the control group, the expression of SHIP and IKβ protein significantly increased, IKK and AKT protein significantly decreased in the immature dendritic cell group (P < 0.05). Compared with the control group, the expression of SHIP and IKK protein significantly decreased, AKT and IKβ protein expression significantly increased in the cyclosporine group (P < 0.05). (5) Results confirm that immature dendritic cells can slow down the severe acute rejection, delay the survival time of liver and reduce the T cell immune response ability of allogeneic liver transplantation.