Mechanism Of Xenograft Heart Transplantation And Complement Inhibition With Anti-C5 Monoclonal Antibody As Well As Combinated With CsA And CyP Prevent Hyperacute Rejection Of Discordant Heart Transplantation

Bachground: Severe end-stage heart disease is very difficult to be treated with current methods. The mortality of those patients is over 85%. Heart transplantation is the most effective method to treat those patients. But severe shortage of donor heart prevents its clinical application. Xenotransplantation offers the possibility of an unlimited supply of heart that could be available electively when required. However, antibody mediated hyperacute rejection provide the main immunologic barriers that have not been overcome. Most clinical xenograft heart died from hyperacute rejection within several hours. There are 4 major immunologic barriers in xenotransplantation, namly, hyperacute rejection, acute vascular rejection, acute cellular rejection and chronic rejection. HAR is mediated by xeno-antibody and activated complement. C5,C3 as well as C1 are major complements that initiate HAR of discordant transplantation. How to overcome the HAR should be solved firstly in research and clinical application of xenotransplantation. DXR/AVR is occurred within several days when the HAR is prevented. There are different reports in mechanism of DXR/AVR, most reports show that DXR is mainly initiated by cellular immune response, include T cell, CD4~+ cell, CD8~+ cell, NK cell and macrophages. Although there are several methods to inhibit activation of complement,...