Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.
Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.
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DOI：
10.1172/jci15888
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
Y. Weiss;A. Maloyan;J. Tazelaar;Nichelle Raj;C. Deutschman
中科院分区：
文献类型：
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作者：
Y. Weiss;A. Maloyan;J. Tazelaar;Nichelle Raj;C. Deutschman
急性呼吸窘迫综合征(ARDS)引起三个病理过程：无节制的炎症、间质/肺泡蛋白积聚和肺上皮细胞的破坏。高度保守的热休克蛋白HSP-70可以限制所有三种反应，但在盲肠结扎和双重穿刺术(2CLP)后，肺组织中没有适当的表达，这是一种临床相关的ARDS模型。我们推测，用腺病毒介导的基因治疗恢复HSP-70的表达将限制2CLP后的肺部病理。我们将含有CMV启动子驱动的猪HSP-70基因的载体(AdHSP)注入2CLP或假手术大鼠的肺内。免疫组织化学和Western印迹杂交显示，假手术或2CLP后给予AdHSP均可增加肺组织中HSP-70蛋白的表达。与对照组相比，注射AdHSP显著减轻了间质和肺泡的水肿和蛋白质渗出，并显著减少了中性粒细胞的聚集。48小时内与CLP相关的死亡率降低了一半。调节HSP-70的产生可以减少实验性ARDS的病理变化，并可能改善预后。
The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.