Sandrin M S, Fodor W L, Mouhtouris E, Osman N, Cohney S, Rollins S A, Guilmette E R, Setter E, Squinto S P, McKenzie I F
Molecular Immunogenetics Laboratory, Austin Research Institute, Heidelberg, Vic., Australia.
Nat Med. 1995 Dec;1(12):1261-7. doi: 10.1038/nm1295-1261.
The major obstacle to successful discordant xenotransplantation is the phenomenon of hyperacute rejection (HAR). In the pig-to-primate discordant transplant setting, HAR results from the deposition of high-titre anti-alpha-galactosyl antibodies and complement activation leading to endothelial cell destruction and rapid graft failure. To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Gal alpha-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the alpha-1,2-fucosyl lactosamine moiety (H-epitope). Xenogenic cells expressing the human alpha-1,2-fucosyltransferase expressed high levels of the H-epitope and significantly reduced Gal alpha-1,3-Gal expression. As a result, these cells were shown to be resistant to human natural antibody binding and complement-mediated cytolysis.
成功进行非协调性异种移植的主要障碍是超急性排斥反应（HAR）现象。在猪到灵长类动物的非协调性移植中，HAR是由高滴度抗α-半乳糖基抗体的沉积和补体激活导致内皮细胞破坏及移植物迅速衰竭引起的。为克服HAR，我们开发了一种酶促碳水化合物重塑策略，旨在用非抗原性的通用供体人类O型血抗原（α-1,2-岩藻糖基乳糖胺部分，即H抗原表位）取代猪细胞表面的Galα-1,3-Gal异种抗原表位的表达。表达人α-1,2-岩藻糖基转移酶的异种细胞高水平表达H抗原表位并显著降低Galα-1,3-Gal的表达。结果，这些细胞显示出对人类天然抗体结合和补体介导的细胞溶解具有抗性。
