Xenotransplantation
Xenotransplantation
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DOI：
10.1096/fasebj.8.14.7958617
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发表时间：
1994-11
期刊：
影响因子：
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通讯作者：
Christopher Y. Lu;T. Khair‐El‐Din;I. Dawidson;T. Butler;Kathleen M. Brasky;Miguel A. Vazquez;S. C. Sicher
中科院分区：
文献类型：
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作者：
Christopher Y. Lu;T. Khair‐El‐Din;I. Dawidson;T. Butler;Kathleen M. Brasky;Miguel A. Vazquez;S. C. Sicher
将猪的实体器官（心脏、肺、肝脏和肾脏）移植到人类身上将解决目前这些器官终末期疾病患者所需的尸体器官严重短缺的问题。此外，远缘物种之间的移植（不一致异种移植）将需要了解许多独特的免疫学特征。不一致的异种移植物在移植后几分钟到几小时内就会被排斥。这种排斥是由于接受者之前从未接触过异种移植物的自然免疫力所致。在某些物种组合中，这种暴发性排斥是由于天然存在的针对异种移植内皮的抗体所致。在其他物种组合中，异种移植物激活补体替代途径。猪与人类的物种组合在临床上最相关。在这种组合中，天然人类和私人抗体识别糖蛋白和糖脂的α-半乳糖基残基。未来预防自然免疫的潜在治疗措施包括将人类补体抑制剂基因工程植入猪细胞膜或对负责将α-半乳糖基残基放置在猪细胞表面的酶进行基因“敲除”。针对异种移植物的获得性免疫也有特殊的考虑因素。细胞因子和粘附分子可能无法跨物种发挥作用。异种移植抗原可能必须由宿主抗原呈递细胞处理，才能有效刺激免疫系统。-Lu, C. Y.、Khair-El-Din, T.、Dawidson, I. A.、Butler, T. M.、Brasky, K. M.、Vazquez, M. A.、Sicher, S. C. 异种移植。 FASEB J. 8, 1122‐1130 (1994)
Transplantation of solid organs (heart, lung, liver, and kidney) from swine to humans would solve the current critical shortage of cadaver organs needed by patients with end‐stage disease of these organs. In addition, transplantation between distant species (discordant xenografting) will require an understanding of a number of unique immunologic features. Discordant xenografts are rejected within minutes to hours after transplantation. This rejection is due to natural immunity by recipients never before exposed to the xenografts. In some species combinations, this fulminant rejection is due to naturally occurring pre‐existing antibodies against the xenograft endothelium. In other species combinations, the xenograft activates the alternative pathway of complement. The swine to human species combination is the most clinically relevant. In this combination, natural human and private antibodies recognize alpha‐galactosyl residues of glycoproteins and glycolipids. Potential future therapeutic measures to prevent natural immunity include the genetic engineering of human complement inhibitors into swine cell membranes or genetic “knock out” of the enzymes responsible for placing alpha‐galactosyl residues on swine cell surfaces. There are also special considerations in acquired immunity against xenografts. Cytokines and adhesion molecules may not work across species lines. Xenograft antigens may have to be processed by host antigen‐presenting cells in order to effectively stimulate the immune system.—Lu, C. Y., Khair‐El‐Din, T., Dawidson, I. A., Butler, T. M., Brasky, K. M., Vazquez, M. A., Sicher, S. C. Xenotransplantation. FASEB J. 8, 1122‐1130 (1994)