Expression of complement regulatory proteins in accommodated xenografts induced by anti-α-Gal IgG1 in a rat-to-mouse model
Expression of complement regulatory proteins in accommodated xenografts induced by anti-α-Gal IgG1 in a rat-to-mouse model
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DOI：
10.1111/j.1600-6143.2007.02016.x
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发表时间：
2008-01-01
影响因子：
8.8
通讯作者：
Chong, A. S.
中科院分区：
文献类型：
--
作者：
Ding, J. Wen;Zhou, T.;Chong, A. S.
抗移植物抗体通常与移植物排斥有关。在特殊条件下，即使存在抗移植物抗体和补体，移植物也能继续正常发挥功能。这种情况被称为住宿。我们开发了一种异种移植调节模型，将刘易斯幼鼠心脏移植到Rag/GT缺陷小鼠体内，通过反复静脉注射低剂量抗α-Gal IgG诱导调节（1）。接受抗α-Gal IgG大剂量注射的移植物存活下来（1），而新鲜移植的第二个移植物被排斥。为了研究抗α-Gal IgG（1）介导的调节机制，实时PCR和免疫组织化学染色均显示调节移植物中的CD 59、Crry和CD 59表达升高。大鼠内皮细胞在体外暴露于抗α-Gal IgG（1）也诱导了CD 14、Crry和CD 59的上调，如Western印迹分析所示，并与体外获得性抗体和补体介导的溶解相关。总的来说，这些研究表明，补体调节蛋白的上调可能会消除补体介导的排斥反应，并允许异种移植物的发展。
Anti-graft antibodies are often associated with graft rejection. Under special conditions, grafts continue to function normally even in the presence of anti-graft antibodies and complement. This condition is termed accommodation. We developed a xenograft accommodation model in which baby Lewis rat hearts are transplanted into Rag/GT-deficient mice, and accommodation is induced by repeated i.v. injections of low-dose anti-alpha-Gal IgG(1). The accommodated grafts survived a bolus dose of anti-alpha-Gal IgG(1), while freshly transplanted second grafts were rejected. To study the mechanism of anti-alpha-Gal IgG(1)-mediated accommodation, both real-time PCR and immunohistochemical staining revealed elevated expression of DAF, Crry and CD59 in the accommodated grafts. In vitro exposure of rat endothelial cells to anti-alpha-Gal IgG(1) also induced the up-regulation of DAF, Crry and CD59, as revealed by Western blot analyses, and was associated with an acquired resistance to antibody and complement-mediated lysis in vitro. Collectively, these studies suggest that the up-regulation of complement regulatory proteins may abrogate complement-mediated rejection and permit the development of xenograft accommodation.