Chen R H, Naficy S, Logan J S, Diamond L E, Adams D H
The Primate Xenotransplantation Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.
Xenotransplantation. 1999 Aug;6(3):194-200. doi: 10.1034/j.1399-3089.1999.00017.x.
We have previously created transgenic pigs bearing the human complement regulatory proteins CD59 and decay-accelerating factor (DAF) by either the intercellular transfer or the cDNA transgenic method. To achieve more physiologic protein expression, we constructed a new line of transgenic pigs with CD59 and DAF human genomic clones. We transplanted these CD59/DAF transgenic pig hearts into baboons immunosuppressed with cyclosporine, methylprednisone or leflunomide/mofetil mycophenolate. The four wild-type hearts survived for 20-80 min, whereas the four CD59/DAF hearts functioned for 85-130 h. Immunohistochemical staining showed levels of CD59 and DAF protein expression similar to that in human hearts. Wild-type and transgenic hearts demonstrate a similar level of IgM deposition, although transgenic hearts suffered less hyperacute rejection and thus less membrane attack complex deposition. The histology of the transgenic grafts after explant was consistent with acute vascular rejection, with a high level of IgG deposit compared with wild-type control. We conclude that this new line of CD59/DAF transgenic pigs express high levels of the transgene products, which conferred longer survival because of better protection from hyperacute rejection. Similar to previous transgenic pigs, however, these animals suffered from delayed xenograft rejection.
我们之前通过细胞间转移或cDNA转基因方法培育出了携带人类补体调节蛋白CD59和衰变加速因子（DAF）的转基因猪。为了实现更接近生理状态的蛋白表达，我们构建了一个携带CD59和DAF人类基因组克隆的新型转基因猪品系。我们将这些CD59/DAF转基因猪的心脏移植到用环孢素、甲泼尼龙或来氟米特/吗替麦考酚酯免疫抑制的狒狒体内。四颗野生型心脏存活了20 - 80分钟，而四颗CD59/DAF心脏功能维持了85 - 130小时。免疫组织化学染色显示CD59和DAF蛋白表达水平与人类心脏相似。野生型和转基因心脏显示出相似水平的IgM沉积，尽管转基因心脏遭受的超急性排斥反应较少，因此膜攻击复合物沉积也较少。移植后取出的转基因移植物的组织学表现与急性血管排斥反应一致，与野生型对照相比，IgG沉积水平较高。我们得出结论，这个新型CD59/DAF转基因猪品系表达高水平的转基因产物，由于对超急性排斥反应有更好的保护作用，从而延长了存活时间。然而，与之前的转基因猪类似，这些动物也遭受了延迟性异种移植排斥反应。
