[Animal transgenesis for necessities of xenotransplantation].
The presence in humans of xenoreactive antibodies directed against swine Gal antigen present on the surface of xenograft donor cells, leads to the complement activation and immediate xenograft rejection--as a consequence of hyperacute immunological reaction. The graft of genetically modified organ of a swine depleted of at alpha1,3-galactosylotransferase enzyme that is responsible for Gal antigen origin, would be tolerated with simultaneous administration of medicines decreasing other less severe immunological reactions. To prevent hyperacute rejection it is also possible to modify swine genome by human genes controlling enzymatic cascade of complement or modifying the set of donor's cell surface proteins. The removal or significant reduction of number of Gal antigen molecules prevents complement activation. In this situation, the main reason for the graft rejection is malfunction of the regulation of coagulation system inside the graft and cellular reactions involving macrophages, neutrophiles, NK cells and lymphocytes T. Minor genetic differences between the acceptor's organism and the donor of grafting organ can lead to so called delayed xenograft rejection. As our knowledge about reactions taking place inside grafted tissue will increase it would be possible to introduce genes controlling coagulation system into swine genome.
Lipiński
Daniel
D
Instytut Genetyki Człowieka PAN, Strzeszyńska 32, 60-479 Poznań. Lipin1@poczta.onet.pl
Zeyland
Joanna
J
Słomski
Ryszard
R
D000818:Animals; D030801:Animals, Genetically Modified; D004187:Disaccharides / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D013045:Species Specificity; D013552:Swine / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*
D004187:Disaccharides; C055075:galactosyl-(1-3)galactose