ICAM-1 expression on bronchial epithelium after recombinant adenovirus infection.
ICAM-1 expression on bronchial epithelium after recombinant adenovirus infection.
复制标题
重组腺病毒感染后支气管上皮上 ICAM-1 的表达。
DOI：
10.1165/ajrcmb.12.2.7865213
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Albelda,SM
中科院分区：
文献类型：
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作者：
Pilewski,JM;Sott,DJ;Wilson,JM;Albelda,SM
早期使用重组腺病毒将基因转移到气道上皮的经验表明，这些载体与炎症的发展有关。其机制尚不清楚，但以前的工作表明，呼吸道病毒可导致气道上皮细胞上细胞间粘附分子-1（ICAM-1）表达增加。因此，我们假设重组腺病毒可能诱导ICAM-1的表达，从而促进气道炎症的发展。为了解决这个问题，原代培养的人支气管上皮细胞的ICAM-1的表达进行了检查，通过流式细胞术感染后的血清型5，E1/E3缺失的重组腺病毒含有大肠杆菌LacZ报告基因驱动的巨细胞病毒启动子（Ad.CMVlacZ）。与对照细胞相比，ICAM-1表达在Ad.CMVlacZ感染后无变化，但在野生型腺病毒感染后增加。用干扰素-γ（IFN）处理Ad. CMVlacZ感染的细胞导致ICAM-1表达增加，但低于单独用IFN处理的细胞中所见的水平，表明重组腺病毒感染减弱IFN诱导的ICAM-1上调。人白细胞与人支气管上皮细胞的粘附在Ad.CMVlacZ感染后没有增加，从而排除了白细胞-上皮粘附的ICAM-1非依赖性增加。ICAM-1表达的结果在体内得到证实，因为用Ad.CMVlacZ感染的人支气管异种移植物的免疫染色显示基底上皮细胞被ICAM-1染色，但在表达β-半乳糖苷酶的细胞上没有增加表达。这项研究表明，与其他呼吸道病毒，重组E1/E3缺失腺病毒不会导致增加ICAM-1表达的人支气管上皮细胞在体外或体内，也不会增加白细胞粘附在体外。
Early experience with recombinant adenoviruses for gene transfer to airway epithelium suggests that these vectors are associated with the development of inflammation. The mechanisms for this are unclear, but previous work has shown that respiratory viruses can cause increased expression of intercellular adhesion molecule-1 (ICAM-1) on airway epithelial cells. We therefore hypothesized that recombinant adenoviruses may induce ICAM-1 expression and thereby facilitate the development of airway inflammation. To address this, primary cultures of human bronchial epithelial cells were examined for ICAM-1 expression by flow cytometry after infection with a serotype 5, E1/E3-deleted recombinant adenovirus containing the Escherichia coli LacZ reporter gene driven by the cytomegalovirus promoter (Ad.CMVlacZ). Compared with control cells, ICAM-1 expression was unchanged after infection with Ad.CMVlacZ, but increased after infection with wild-type adenovirus. Treatment of Ad.CMVlacZ-infected cells with interferon-gamma (IFN) resulted in increased ICAM-1 expression, but to a lower level than that seen in cells treated with IFN alone, indicating that recombinant adenovirus infection blunted IFN-induced up-regulation of ICAM-1. Adhesion of human leukocytes to human bronchial epithelial cells was not increased after Ad.CMVlacZ infection, thereby excluding an ICAM-1-independent increase in leukocyte-epithelial adhesion. The results for ICAM-1 expression were confirmed in vivo, as immunostaining of human bronchial xenografts infected with Ad.CMVlacZ revealed basilar epithelial staining with ICAM-1, but no increased expression on cells expressing beta-galactosidase. This study demonstrates that unlike other respiratory viruses, recombinant E1/E3-deleted adenovirus does not cause increased ICAM-1 expression on human bronchial epithelium in vitro or in vivo nor increased leukocyte adhesion in vitro.