Targeting type II and Clara cells for adenovirus-mediated gene transfer using the surfactant protein B promoter.
Targeting type II and Clara cells for adenovirus-mediated gene transfer using the surfactant protein B promoter.
复制标题
使用表面活性蛋白 B 启动子靶向 II 型和 Clara 细胞进行腺病毒介导的基因转移。
DOI：
10.1165/ajrcmb.18.1.2878
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Ballard,PL
中科院分区：
文献类型：
--
作者：
Strayer,MS;Guttentag,SH;Ballard,PL
We examined the ability of the human surfactant protein B (SP-B) promoter to confer cell specificity of transgene expression in an adenoviral vector. Using similar replication-deficient adenoviruses (rAd), we comparedlacZreporter gene expression driven by the human SP-B promoter (rAd.SPBlacZ) with the ubiquitously expressed Rous sarcoma virus promoter (rAd.RSVlacZ). rAd.SPBlacZ expressedlacZin H-441 and A549 lung epithelial cell lines and not in HeLa cells whereas rAd.RSVlacZ expressed in all three cell lines. In primary human fetal lung fibroblasts, β-galactosidase activity from rAd.RSVlacZ transduction increased in a dose-dependent manner whereas activity from rAd.SPBlacZ remained low. In mixed cell cultures prepared from human fetal lung explants that contained fibroblasts and type II cells, X-Gal staining localized rAd.SPBlacZ expression to only type II cells whereas rAd.RSVlacZ expressed in both cell types. In 24-wk gestation human fetal tissue explants infectedex vivo, the RSV promoter directedlacZexpression in lung, trachea, heart, liver, and esophagus, whereas with the SP-B promoterlacZwas expressed only in lung, specifically in air space-lining cells. This specificity was maintainedin vivo.lacZexpression was undetectable in lung and other tissues after intravenous administration of rAd.SPBlacZ whereas rAd.RSVlacZ expressed primarily in liver. After intratracheal instillation of rAd.SPBlacZ into mice, X-Gal staining localized expression to type II and Clara cells. In contrast, rAd.RSVlacZ expressed in all pulmonary epithelial cell types. Our results indicate that the SP-B promoter may be useful in targeting type II and Clara cells for gene therapy of conditions such as inherited deficiency of SP-B.
