Collins B H, Cotterell A H, McCurry K R, Alvarado C G, Magee J C, Parker W, Platt J L
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 1995 May 15;154(10):5500-10.
Transplants performed between phylogenetically disparate species are subject to hyperacute rejection initiated by binding of xenoreactive natural Abs to endothelium in the donor organ. Binding of these Abs activates complement, leading to tissue injury and destruction of the graft. Human xenoreactive natural Abs recognize Gal alpha 1-3Gal beta 1-4GlcNAc (galactose alpha 1-3galactose beta 1-4-N-acetylglucosame); however, the relative importance of this Ag in graft rejection has not been proved. The present study was conducted to test the potential importance of alpha-galactosyl (alpha-Gal) determinants in the pathogenesis of hyperacute rejection. To this end, hearts (n = 3) from New World monkeys (Saimiri scureus, squirrel monkey), which can synthesize Gal alpha 1-3Gal, were transplanted heterotopically into Old World monkeys (Papio species, baboon), which do not synthesize Gal alpha 1-3Gal determinants and which have circulating anti-alpha Gal Abs. The xenografts were rejected in 51 to 56 min (mean +/- SD = 53.3 +/- 2.5), results similar to those observed in porcine grafts transplanted into baboons. Histologic analysis of the hearts revealed thrombosis and intraparenchymal hemorrhage and immune deposits consisting of IgM, Clq, C3, C4, C5b, and the membrane attack complex, but not properdin or factor B of the recipient deposited on graft endothelium. Sera obtained from baboons after perfusion of squirrel monkey kidneys revealed depletion of alpha-Gal-specific Abs and anti-pig endothelial cell Abs. These findings provide strong evidence that the Abs that accumulate in New World monkey organs during perfusion with baboon blood are the same Abs that would accumulate in a porcine organ transplanted into a primate and suggest that hyperacute rejection is not necessarily a reflection of phylogenetic distance but that the expression of terminal alpha-Gal residues provides an adequate target to initiate that process.
在系统发育关系差异较大的物种之间进行的移植会发生超急性排斥反应，其起始过程是异种反应性天然抗体与供体器官的内皮细胞结合。这些抗体的结合会激活补体，导致组织损伤和移植物破坏。人类异种反应性天然抗体可识别半乳糖α1-3半乳糖β1-4N-乙酰葡糖胺（Galα1-3Galβ1-4GlcNAc）；然而，这种抗原在移植物排斥反应中的相对重要性尚未得到证实。本研究旨在测试α-半乳糖基（α-Gal）决定簇在超急性排斥反应发病机制中的潜在重要性。为此，将能够合成Galα1-3Gal的新大陆猴（松鼠猴，Saimiri scureus）的心脏（n = 3）异位移植到不能合成Galα1-3Gal决定簇且具有循环抗α-Gal抗体的旧大陆猴（狒狒属，狒狒）体内。异种移植物在51至56分钟内被排斥（平均值±标准差= 53.3±2.5），结果与将猪移植物移植到狒狒体内时观察到的结果相似。对心脏的组织学分析显示有血栓形成、实质内出血以及由IgM、Clq、C3、C4C5b和膜攻击复合物组成的免疫沉积物，但没有备解素或受体的B因子沉积在移植物内皮上。用松鼠猴肾脏灌注狒狒后获得的血清显示α-Gal特异性抗体和抗猪内皮细胞抗体减少。这些发现提供了强有力的证据，表明在用狒狒血液灌注期间在新大陆猴器官中积累的抗体与在移植到灵长类动物体内的猪器官中积累的抗体相同，并表明超急性排斥反应不一定反映系统发育距离，而是末端α-Gal残基的表达提供了启动该过程的合适靶点。
