Yokoyama H, Naito T, Wada T, Kelley V R
Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA.
Exp Nephrol. 1999 May-Jun;7(3):267-72. doi: 10.1159/000020612.
We constructed an ex vivo gene transfer system to deliver cytokines into the kidney and circulation using genetically modified renal tubular epithelial cells (TEC). TEC were infected with recombinant retroviruses expressing macrophage (Mphi) growth factors using a retroviral Moloney murine leukemia virus-based MFG vector. These infected TEC have the capacity to secrete stable and sustained amounts of cytokines for prolonged periods (>4 months) in vitro and in vivo (>28 days). Implanting genetically modified TEC secreting Mphi growth factors under the kidney capsule initiates severe local renal injury in mice with a deficiency in Fas (Faslpr gene). This system offers a novel and powerful approach to probe for the impact of sustained cytokine expression in the progression of kidney destruction.
我们构建了一种体外基因转移系统，利用基因改造的肾小管上皮细胞（TEC）将细胞因子输送到肾脏和循环系统中。使用基于逆转录病毒莫洛尼鼠白血病病毒的MFG载体，用表达巨噬细胞（Mphi）生长因子的重组逆转录病毒感染TEC。这些被感染的TEC能够在体外长时间（>4个月）和体内（>28天）分泌稳定且持续量的细胞因子。在Fas（Faslpr基因）缺陷的小鼠肾包膜下植入分泌Mphi生长因子的基因改造TEC会引发严重的局部肾损伤。该系统为探究持续细胞因子表达在肾脏破坏进展中的影响提供了一种新颖且强大的方法。
