Low Molecular Weight Dextran Sulfate Inhibits The Complement Activity And Prevent Hyper Acute Rejection In Xenotransplantation Model

PartⅠLow molecular weight dextran sulfate inhibits human complement activityObjective To investigate the effect of low-molecular weight dextran sulfate (DXS, molecular weight 5000) on human complement activityMethods CH50 test was chosen to test the complement activity of the pooled normal human B-type serum in addition of different concentration of DXS (0.1mg/ml, 0.5mg/ml, 1mg/ml, 2mg/ml, 4mg/ml). MTT test was chosen to evaluate the cytotoxicity of human serum in addition of different concentration of DXS against PEC. Human serum without DXS served as control. Immunoflurescence staining was chosen to detect the deposition of complement C3c and anti-human IgM,IgG antibodies on the PEC surface.Results DXS dose-dependently inhibit the human serum complement activity and inhibit the cytotoxity of human serum against PEC. Compared to the control group, complement C3c deposition on the PEC surface were decreased. Significant differences of anti-human IgM,IgG antibodies deposition could not be detected.Conclusion Low-molecular weight dextran sulfate could effectively inhibit the human complement activity. PartⅡLow molecular weight dextran sulfate prevent hyperacute rejection in xenotransplantation modelObjective To investigate the effect of low-molecular weight dextran sulfate (DXS, molecular weight 5000)on human complement activation and prevent hyperacute rejection in ex vivo human serum perfusion model.Methods The hearts of balbc mice were isolated and perfused with 10% pooled human serum of B type to which 0.1mg/ml or 2 mg/ml DXS were added. 10% pooled human serum without DXS were served as control proup. Heart beating was monitored and immunoflurescence staining and immunohistochemistry were chosen to detect the deposition of complement C3c,C5b-9.Results In the ex vivo perfusion experiment, the mean survival time of hearts perfused without DXS was 17±11min. Addition of DXS prolonged heart survival to 49±15min for 0.1mg/ml and 123±19min for 2mg/ml. The deposition of complement C3c,C5b-9 were significantly decreased in experimental group.Conclusion Low-molecular weight dextran sulfate effectively inhibits the complement activity and prevent the hyperacute rejection in xenotransplantation.