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猪组织中与人类天然抗体发生反应的碳水化合物抗原,作为猪到人的器官异种移植中超急性血管排斥反应的潜在靶点。

Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for hyperacute vascular rejection in pig-to-man organ xenotransplantation.

作者信息

Oriol R, Ye Y, Koren E, Cooper D K

机构信息

INSERM U.178, Villejuif, France.

出版信息

Transplantation. 1993 Dec;56(6):1433-42. doi: 10.1097/00007890-199312000-00031.

DOI:10.1097/00007890-199312000-00031
PMID:8279016
Abstract

Pig tissues were screened by immunofluorescence with lectins, mAb, and human natural antibodies for the presence of carbohydrate antigens, which may be potential targets for hyperacute vascular rejection in pig to man xenotransplantation. The unfucosylated monomorph linear B-antigen was found at the surface of all porcine vascular endothelial cells. This pig linear-B antigen reacts strongly with the anti-alpha Gal isolectin B4 from Griffonia simplicifolia 1 and with human natural anti-alpha Gal antibodies specifically purified by affinity chromatography on synthetic oligosaccharides containing the terminal nonreducing alpha Gal1-->3 beta Gal-R disaccharide. This antigenic activity is destroyed by treatment of pig tissues with alpha-galactosidase. The localization of this linear-B epitope on vascular endothelium and its reactivity with natural human anti-alpha Gal antibodies suggest that it may play a major role in the hyperacute vascular rejection of pig to man organ xenografts. The lectin from Maackia amurensis reacting with alpha NeuAc2-->3 beta Gal1-->4GlcNAc/Glc was also positive on pig vascular endothelium, but we do not know yet whether there are human natural antibodies reacting with the carbohydrate recognized by this lectin. Epithelial cells of pig renal proximal convoluted tubules, respiratory epithelium, pancreatic ducts, and epidermis express the linear-B antigen, but they are less likely to trigger a hyperacute vascular rejection because they are not directly exposed to the blood. The genetically defined pig A+/A- system controls the expression of A and H antigens in pig epithelial cells from renal distal and collecting tubules, biliary ducts, pancreatic ducts, large bronchi, and digestive mucosa. The pig A antigen may trigger an immune response in human O or B recipients if they are transplanted with organs from A+ pigs, but the pig A antigen is probably not involved in the hyperacute vascular rejection of a xenograft because it is not expressed on vascular endothelium.

摘要

用凝集素、单克隆抗体和人类天然抗体通过免疫荧光法对猪组织进行筛选,以检测碳水化合物抗原的存在,这些抗原可能是猪到人异种移植中超急性血管排斥反应的潜在靶点。在所有猪血管内皮细胞表面均发现了未岩藻糖基化的单态线性B抗原。这种猪线性B抗原与来自西非豆科植物种子的抗αGal异凝集素B4以及通过在含有末端非还原αGal1→3βGal-R二糖的合成寡糖上进行亲和层析特异性纯化的人类天然抗αGal抗体发生强烈反应。用α-半乳糖苷酶处理猪组织可破坏这种抗原活性。这种线性B表位在血管内皮上的定位及其与人类天然抗αGal抗体的反应性表明,它可能在猪到人器官异种移植的超急性血管排斥反应中起主要作用。与αNeuAc2→3βGal1→4GlcNAc/Glc反应的山嵛菜凝集素在猪血管内皮上也呈阳性,但我们尚不清楚是否存在与该凝集素识别的碳水化合物发生反应的人类天然抗体。猪肾近端曲管的上皮细胞、呼吸道上皮、胰管和表皮表达线性B抗原,但它们不太可能引发超急性血管排斥反应,因为它们不直接接触血液。基因定义的猪A+/A-系统控制猪肾远端和集合管、胆管、胰管、大气道和消化黏膜上皮细胞中A和H抗原的表达。如果将来自A+猪的器官移植给人类O型或B型受体,猪A抗原可能会引发免疫反应,但猪A抗原可能不参与异种移植的超急性血管排斥反应,因为它不在血管内皮上表达。

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