Effect of adenoviral vector infection on cell proliferation in cultured primary human airway epithelial cells.
Effect of adenoviral vector infection on cell proliferation in cultured primary human airway epithelial cells.
复制标题
腺病毒载体感染对培养的原代人气道上皮细胞增殖的影响。
DOI：
10.1089/hum.1995.6.8-1045
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Boucher,RC
中科院分区：
文献类型：
--
作者：
Teramoto,S;Johnson,LG;Huang,W;Leigh,MW;Boucher,RC
尽管重组腺病毒被用作将治疗基因递送至囊性纤维化（CF）患者气道的载体，但这些载体对气道上皮细胞生长动力学的影响尚未得到研究。我们测试了 E1、E3 缺失的 Ad 载体 (Ad5-CMV-lacZ) 是否影响原代培养中人气道上皮细胞的细胞增殖动力学。载体感染复数（moi）与Ad介导的lacZ基因转移效率之间存在剂量依赖性关系。与载体相比，暴露于载体的细胞的生长曲线以剂量依赖性方式向右移动。载体诱导的细胞增殖减慢是由于（i）凋亡细胞死亡增加和（ii）S期募集减少造成的。载体基因的紫外线灭活消除了对细胞增殖的影响。这些数据表明，随着载体的moi增加以实现有效的基因转移，受感染细胞的细胞凋亡和细胞周期减慢也随之增加。这些载体对人气道细胞的作用的鉴定和灭活对于降低用于CF气道基因治疗的腺病毒载体的毒性可能很重要。
Although recombinant adenoviruses are used as vectors for delivering therapeutic genes to the airways of cystic fibrosis (CF) patients, the effects of these vectors on the kinetics of airway epithelial cell growth have not been investigated. We tested whether E1, E3-deleted Ad vectors (Ad5-CMV-lacZ) affect the kinetics of cell proliferation of human airway epithelial cells in primary culture. There was a dose-dependent relationship between the vector multiplicity of infection (moi) and the efficiency of Ad-mediatedlacZgene transfer. Growth curves of cells exposed to vector were shifted to the right as compared to vehicle in a dose-dependent manner. The vector-induced slowing of cell proliferation resulted from both (i) increased apoptotic cell death and (ii) lower recruitment into S phase. UV inactivation of the vector genes abolished the effects on cell proliferation. These data demonstrate that as the moi of vectors is increased to achieve effective gene transfer, apoptosis and slowing of the cell cycle of infected cells increases concomitantly. The identification and inactivation of these vector effects on human airway cells may be important for reducing the toxicity of adenovirus vectors for gene therapy of CF airways.