Cellular and molecular mechanisms regulating silica-induced adhesion molecule expression in mice.
Cellular and molecular mechanisms regulating silica-induced adhesion molecule expression in mice.
复制标题
调节二氧化硅诱导的小鼠粘附分子表达的细胞和分子机制。
DOI：
10.1615/jenvironpatholtoxicoloncol.v20.isuppl.1.40
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
C. Giardina
中科院分区：
文献类型：
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作者：
A. Hubbard;M. Thibodeau;C. Giardina
小鼠暴露于二氧化硅颗粒会产生强烈的炎症反应，其特征是中性粒细胞和单核细胞涌入肺泡，导致细胞活化。这些细胞运输和效应器功能部分由不同家族的粘附分子介导。一种这样的粘附蛋白，细胞间粘附分子-1（ICAM-1），在多种细胞上表达，包括血管内皮细胞、成纤维细胞、I型和II型肺泡上皮细胞、一些淋巴细胞和单核细胞/巨噬细胞。在过去的几年里，我们的实验室一直专注于二氧化硅诱导的ICAM-1表达暴露小鼠（体内）和细胞（体外），通过检查这种粘附蛋白对肺细胞的作用和调节。我们已经确定，小鼠气管内暴露于二氧化硅（每只小鼠2毫克）elevently增加ICAM-1的表达肺巨噬细胞和肺实质内的II型上皮细胞，支气管肺泡灌洗液巨噬细胞，并作为一种可溶性蛋白在灌洗液。我们推测ICAM-1表达的增加可能参与二氧化硅诱导的中性粒细胞流入肺泡，以及巨噬细胞来源的炎性信号，负责中性粒细胞的迁移。活性氧（ROS）和肿瘤坏死因子-α（TNF-α）增强了暴露于二氧化硅的小鼠巨噬细胞上的ICAM-1表达，并且似乎通过ICAM-1启动子内的特定序列元件进行调节。
Exposure of mice to silica particles generates an intense inflammatory response characterized by the influx of neutrophils and monocytes into the alveoli with resulting cell activation. These cell trafficking and effector functions are, in part, mediated by different families of adhesion molecules. One such adhesion protein, intercellular adhesion molecule-1 (ICAM-1), is expressed on a variety of cells including vascular endothelial cells, fibroblasts, types I and II alveolar epithelial cells, some lymphocytes, and monocytes/macrophages. Over the last several years, our laboratory has focused on silica-induced ICAM-1 expression in exposed mice (in vivo) and cells (in vitro) by examining the role and regulation of this adhesion protein on pulmonary cells. We have determined that intratracheal exposure of mice to silica (2 mg per mouse) elicits increased expression of ICAM-1 on pulmonary macrophages and type II epithelial cells within the lung parenchyma, on bronchoalveolar lavage macrophages, and as a soluble protein in lavage fluid. We hypothesize that increased ICAM-1 expression mayparticipate in silica-induced neutrophil influx into the alveoli, as well as in macrophage-derived phlogistic signals responsible for migration of neutrophils. ICAM-1 expression on silica-exposed mouse macrophages is enhanced by reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha) and appears to be regulated through specific sequence elements within the ICAM-1 promoter.