McCurry K R, Parker W, Cotterell A H, Weidner B C, Lin S S, Daniels L J, Holzknecht Z E, Byrne G W, Diamond L E, Logan J S, Platt J L
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Hum Immunol. 1997 Dec;58(2):91-105. doi: 10.1016/s0198-8859(97)00229-2.
Organs transplanted between phylogenetically-disparate species, such as from the pig into the primate, are subject to hyperacute and acute vascular rejection. Hyperacute rejection of a porcine organ by a primate is thought to be initiated by the binding of xenoreactive natural antibodies to Galalpha1-3Gal expressed on the endothelial lining of blood vessels in the xenograft. The factor(s) which initiates acute vascular rejection is uncertain; however, there is some evidence implicating xenoreactive antibodies. The nature of the humoral response which might contribute to acute vascular rejection of a porcine organ was investigated in baboons which received a porcine cardiac xenograft plus immunosuppression with methylprednisolone, azathioprine, and cyclosporine. Following rejection and surgical removal of the xenografts, the serum concentration of xenoreactive antibodies increased in untreated animals but in immunosuppressed animals was similar to the concentration in preimmune serum. The antibodies in the sensitized recipients were specific for Galalpha1-3Gal (70-95%) and other determinants (5-30%). However, cross-blocking studies showed that, following xenotransplantation, the immunosuppressed baboons had no detectable IgM or IgG directed against "new" endothelial antigens. These results indicate that antibodies made by immunosuppressed individuals in response to xenotransplantation are much like xenoreactive natural antibodies and suggest that acute vascular rejection might in some cases be addressed by therapeutic strategies aimed at those antibodies.
在系统发育上差异较大的物种之间进行的器官移植，比如从猪到灵长类动物，会遭受超急性和急性血管排斥反应。灵长类动物对猪器官的超急性排斥反应被认为是由异种反应性天然抗体与异种移植物血管内皮上表达的α1-3半乳糖结合引发的。引发急性血管排斥反应的因素尚不确定；然而，有一些证据表明异种反应性抗体与之有关。在接受猪心脏异种移植并使用甲基强的松龙、硫唑嘌呤和环孢素进行免疫抑制的狒狒中，研究了可能导致猪器官急性血管排斥反应的体液反应的性质。在异种移植物被排斥并手术切除后，未治疗动物体内异种反应性抗体的血清浓度升高，但免疫抑制动物体内的浓度与免疫前血清中的浓度相似。致敏受体中的抗体对α1-3半乳糖具有特异性（70-95%），对其他决定簇具有特异性（5-30%）。然而，交叉阻断研究表明，异种移植后，免疫抑制的狒狒体内没有可检测到的针对“新”内皮抗原的IgM或IgG。这些结果表明，免疫抑制个体对异种移植产生的抗体与异种反应性天然抗体非常相似，并表明在某些情况下，急性血管排斥反应可能可以通过针对这些抗体的治疗策略来解决。
