Porcine platelet antigens recognized by human xenoreactive natural antibodies.
Porcine platelet antigens recognized by human xenoreactive natural antibodies.
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猪血小板抗原被人类异种反应性天然抗体识别。
DOI：
10.1097/00007890-199402150-00003
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发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
Holzknecht,ZE
中科院分区：
文献类型：
--
作者：
Platt,JL;Holzknecht,ZE
灵长类动物对猪器官的超急性异种移植排斥反应是由受体天然抗体与供体器官中的内皮细胞结合而引发的。我们先前表明，人天然抗体识别3个猪内皮细胞糖蛋白，分子量为115 kDa，125 kDa和135 kDa;我们称之为糖蛋白gp 115/135。我们还发现，猪血小板含有糖蛋白抗原，是相同或非常相似的gp 115/135从内皮细胞。本文报道的研究旨在鉴定这些猪血小板抗原，并评估其与异种移植物损伤发病机制的潜在相关性。gp 115/135作为人天然抗体靶的重要性得到以下证明的支持：（a）在猪肾灌注期间，抗猪血小板gp 115/135的抗体从非人灵长类动物的血液中被吸收;（B）浓度< 500 pM的纯化gp 115/135糖蛋白阻断人天然抗体与培养的猪内皮细胞的结合;（c）通过从提取物中除去GP 115或GP 135，人抗体与猪血小板提取物的结合显著降低;（d）抗体与GP 115/135的结合启动补体的活化。gp 115/135的氨基末端测序显示，gp 115与人整联蛋白β 3链具有显著同源性，gp 125与人α IIb链具有显著同源性，gp 135与人α 2链具有显著同源性。猪糖蛋白的配体结合特性与通过氨基酸测序和分子量揭示的抗原的身份一致。人天然抗体还识别250 kDa的猪血小板糖蛋白，发现其与人血管性血友病因子（vWF）同源。非人灵长类动物血液中抗vWF的抗体在猪器官的离体灌注期间被吸收。gp 115/135作为整合素的鉴定，其在内皮中的功能可能包括细胞信号传导和屏障功能的维持，提供了对排斥反应的发病机制的潜在洞察，其中这些过程明显异常。vWF作为潜在靶抗原的鉴定提出了几个问题，包括vWF是否为抗体与异种内皮的结合提供了一个基础，或者从内皮细胞分泌后vWF是否可能实际上阻断抗体结合。
Hyperacute xenograft rejection of porcine organs by primates is initiated by the binding of recipient natural antibodies to endothelium in the donor organ. We showed previously that human natural antibodies recognize 3 porcine endothelial cell glycoproteins with molecular masses of 115 kDa, 125 kDa, and 135 kDa; we called the glycoproteins gp115/135. We also showed that porcine platelets contain glycoprotein antigens that are the same or very similar to gp115/135 from endothelial cells. The studies reported here were aimed at identifying these porcine platelet antigens and evaluating their potential relevance for the pathogenesis of xenograft injury. The importance of gp115/135 as targets of human natural antibodies was supported by the demonstration that (a) antibodies against porcine platelet gp115/135 are absorbed from the blood of nonhuman primates during the perfusion of a porcine kidney;(b) purified gp115/135 glycoproteins at concentrations< 500 pM, block the binding of human natural antibodies to cultured porcine endothelial cells;(c) the binding of human antibodies to porcine platelet extracts is significantly decreased by removal of gp115 or gp135 from the extracts;(d) antibody binding to gp115/135 initiates the activation of complement. Amino-terminal sequencing of gp115/135 revealed that gp115 has significant homology to human integrin [beta] 3 chains, gp125 to human [alpha] IIb chains, and gp135 to human [alpha] 2 chains. Ligand binding properties of the porcine glycoproteins were consistent with the identity of the antigens revealed by amino acid sequencing and molecular weight. Human natural antibodies also recognized a 250 kDa porcine platelet glycoprotein which was found to be homologous to human von Willebrand factor (vWF). Antibodies against vWF in the blood of nonhuman primates are absorbed during ex vivo perfusion of a porcine organ. The identification of gp115/135 as integrins, the functions of which in endothelium might include cell signaling and maintenance of barrier function, provides potential insight into the pathogenesis of the rejection reaction in which these processes are manifestly aberrant. The identification of vWF as a potential target antigen raises several questions, including whether vWF provides one basis for antibody binding to xenogeneic endothelium or whether upon secretion from an endothelial cell vWF might actually block antibody binding.