ObjectiveTo investigate the aim antigen coursing the hyperacute rejection of xenotransplantation. MethodsDocuments about hyperacute rejection in xenotransplantation were reviewed and summarized in detail. ResultsPig is thought to be one of the ideal donors of xenotransplantation, but the major obstacle is hyperacute rejection mediated by complement that is activated though human serum. αGal is recognized as the major antigen and its expression is controlled by α1,3 galactosyltransferase. Immunoabsorption of preexsisted antibody, enzymatic digestion of αGal, knockout αGT gene and transgenic technology have been used to solve this problem. Even so, there remain other antigens which can combine with natural antibodies in human serum, such as, 40×103 molecule in erythrocyte, 210×103, 105×103 and 50×103 antigen in pig embryo brain cell, etc. Conclusion αGal is the major antigen which course the hyperacute rejection. Besides αGal, many nonalphagal need further investigation.
Objective To investigate the mechanism of hyperacute rejection (HAR) in pig to rhesus monkey vein xenograft. Methods Porcine femoral vein was transplanted into rhesus monkey. Deposits of IgM, IgG, C3 and C4 on the grafts were observed by immunoflurescence. Results Great deal of IgM, C3 and C4 were seen along the endothelium of donor vein, but IgG was not seen. ConclusionIn pig to monkey xenograft model, HAR is intiated by the binding of xenoreactive IgM to donor xenoantigens and followed by the activation of complement via the classical pathway.
Limitation of donor source for allograft makes the research on xenograft progress. Pig is regarded as one of the ideal donor animals. The major obstacle in xenograft is hyperacute rejection, which is caused by complements after they are activated by xenogeneic antigens combined with natural antibodies. It has been confirmed that alpha-Gal is the major target antigen, whose expression is incharged by alpha-1,3 galactosyltransferase (alpha-GT). The approaches to overcome hyperacute rejection against alpha-Gal included: immunoadsorption of xenogeneic natural antibodies, lysis of antigen by enzyme and genetic manupilation to obtain animal lack of alpha-GT. Besides alpha-Gal, there were other antigens binding to human serum antibody, such as gp65 and gp100, which was expressed on PAEC after induced by TNF, the A-like antigen. But their function was still unknown. It was debatable on the role of MHC in xenograft. Both direct and indirect pathway were involved in cellular response in xenograft.
Insufficient supply of organ for allotransplantation made the study on finding new organ resources from animal progress. Pig is regarded as one of the optimal donor animals for human. The major obstacle in this field is hyperacute reaction (HAR), which is triggered after the xenogenic natural antibodies preexisting in recipient blood combine to the antigens on the surface of the endothelium and activate the complement system. alpha-Galactose residues (alpha-Gal) on the endothelial cell have been identified as the major xenoantigens. NJZ Pig has been closely breed since 1938, whose family history is clear. Tissue samples from heart, liver, kidney, pancreas, lung, small intestine, skin, spleen, thymus and lymph node were obtained and embedded in paraffin. The sections were performed the immunohistochemical staining with the sera from health volunteers (including all the blood types) as the primary antibodies as well as the biotin labeled bandeirae simplicifolia I isolectin B4 (BS I-B4), which has specific affinity to alpha-galactose. All the staining sections were compared with the tissues digested with alpha-galactosidase. There was no difference between the antigens recognized by sera of different blood types. alpha-Gal was still the major xenoantigen on the endothelial cells. There might exist non-alpha-Gal antigens on the distal convoluted tubules and collecting tubules of the kidney. There was no alpha-Gal distributing on the secreting part of pancreas, either the islet cells or the matrix cells, but surely on pancreatic duct and vessels. All the antigenity was destroyed after the enzyme digestion except that the small intestine gland still positive with the BS I-B4. alpha-Gal is the major xenogenic antigen in NJZ Pigs. There exist some unknown antigens on the distal convoluted tubules and collecting ducts of the kidney. The blood type of recipient is not the first affair to be considered in pig-to-human xenotransplantation. The specificity of BS I-B4 for the alpha-galactose needs more detail research.
Objective To summarize the current advance of xenotransplantation. Methods Relevant literatures about current advance of xenotransplantation published recently domestic and abroad were collected and reviewed. Results Major progress of xenotransplantation had been made in the understanding of xenoimmunobiology in the last two decades and in the threshold of clinical application. However, many problems of immunological rejection were still needed to be explored and resolved. Conclusion Xenotransplantation as a transplantation source has an extensive potential to resolve the shortage of transplanted organs for end-stage organ failure, how to suppress rejection and prolong survival of grafts more effectively is a focal point of search in the future.