Anti-Gal antibody-mediated allograft rejection in α1,3-galactosyltransferase gene knockout mice -: A model of delayed xenograft rejection
Anti-Gal antibody-mediated allograft rejection in α1,3-galactosyltransferase gene knockout mice -: A model of delayed xenograft rejection
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DOI：
10.1097/00007890-199809270-00009
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发表时间：
1998-09-27
期刊：
影响因子：
6.2
通讯作者：
D'Apice, AJ
中科院分区：
文献类型：
--
作者：
Pearse, MJ;Witort, E;D'Apice, AJ
背景。抗半乳糖α 1,3半乳糖（抗α Gal）异种抗体在启动超急性异种移植排斥反应中的关键作用已通过各种体外和体内方法清楚地证明。然而，抗α - Gal抗体在介导超急性排斥机制中的作用，如抗体依赖性细胞毒性，仍有待确定，主要是因为缺乏小动物模型来研究这一现象。将野生型小鼠的心脏异位移植到α 1,3-半乳糖转移酶敲除（Gal KO）小鼠体内，使其像人一样产生对α 1,3半乳糖（Gal）的抗体。在发生排斥反应时，对心脏进行组织学检查以确定排斥反应的机制。将野生型小鼠的心脏移植到高滴度抗α - Gal受体中，8-13天后发生排斥反应。组织学检查显示细胞浸润由巨噬细胞（80-90%）、自然杀伤细胞（5-10%）和T细胞（1-5%）组成。相比之下，将野生型心脏移植到低抗gal滴度受体中显示出较长的存活时间（约90天）。然而，这些患者中有很大一部分（30-40%）在10 - 13天内经历了轻微的排斥反应，但随后恢复（“适应”）。本研究结果表明，Gal IFO小鼠是一种有用的小动物血管化同种异体移植模型，在该模型中，抗α - Gal抗体在移植排斥反应中的作用可以与其他排斥机制分离研究。抗α - Gal抗体的滴度被发现是排斥反应的关键决定因素。在细胞浸润的时间和组成方面，该模型的排斥反应的组织病理学特征与其他延迟异种移植排斥反应模型非常相似。因此，Gal KO小鼠提供了一种新的啮齿动物模型，这将有助于识别参与延迟异种移植排斥发病机制的不同成分。
Background. The key role of anti galactose alpha 1,3 galactose (anti-alpha Gal) xenoantibodies in initiating hyperacute xenograft rejection has been clearly demonstrated using a variety of in vitro and in vivo approaches. However, the role of anti-alpha Gal antibodies in mediating post-hyperacute rejection mechanisms, such as antibody-dependent cellular cytoxicity, remains to be determined, primarily because of the lack of a small animal model with which to study this phenomena.Methods. Hearts from wild-type mice were transplanted heterotopically into alpha 1,3-galactosyltransferase knockout (Gal KO) mice, which Like humans develop antibodies to the disaccharide galactose alpha 1,3 galactose (Gal). At the time of rejection, hearts were examined histologically to determine the mechanism of rejection.Results. Hearts from wild-type mice transplanted into high-titer anti-alpha Gal recipients were rejected in 8-13 days. Histological examination demonstrated a cellular infiltrate consisting of macrophages (80-90%), natural killer cells (5-10%), and T cells (1-5%). In contrast, wild-type hearts transplanted into low anti-Gal titer recipients demonstrated prolonged (>90 day) survival. However, a significant proportion (30-40%) of these underwent a minor rejection episode between 10 and 13 days, but then recovered ("accommodated").Conclusions. The results of this study suggest that the Gal IFO mouse is a useful small animal vascularized allograft model, in which the role of anti-alpha Gal antibody in graft rejection can be studied in isolation from other rejection mechanisms. The titer of anti-alpha Gal antibody was found to be the critical determinant of rejection. The histopathological features of rejection in this model are very similar to other models of delayed xenograft rejection, in both the timing and composition of the cellular infiltrate. The Gal KO mouse therefore provides a new rodent model, which will aid in the identification of the distinct components involved in the pathogenesis of delayed xenograft rejection.