Chen F, Kuhn D C, Gaydos L J, Demers L M
Department of Pathology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, USA.
APMIS. 1996 Mar;104(3):176-82. doi: 10.1111/j.1699-0463.1996.tb00705.x.
Nitric oxide (NO), a nitrogen-free radical, plays an important role in mediating inflammatory reaction and cytotoxicity of tissue. To determine whether NO was involved in silica-induced pulmonary tissue damage, we studied the effects of silica on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression by THP-1 cells, a monocyte-like cell line with properties of the pulmonary alveolar macrophage. Experimental results showed that silica elicited a marked stimulation of nitric oxide production in a time-dependent manner by THP-1 cells in vitro following the priming of these cells with the phorbol ester PMA. Both nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMMA) and xanthine oxidase inhibitor allopurinol can partially suppress silica-induced NO production in PMA-primed THP-1 cells. Northern blot analysis indicated that, after 2 h of silica exposure, PMA-primed THP-1 cells began to express iNOS mRNA, which reached peak expression at 8 h. Endotoxin treatment of these cells produced a similar effect. These results indicated that silica is a potent inducer of NO production in macrophages and its ability to induce tissue damage may partially be attributed to its ability to initiate excessive production of nitric oxide from macrophages.
一氧化氮（NO）是一种无氮自由基，在介导炎症反应和组织细胞毒性方面发挥着重要作用。为了确定NO是否参与二氧化硅诱导的肺组织损伤，我们研究了二氧化硅对THP-1细胞（一种具有肺泡巨噬细胞特性的单核细胞样细胞系）一氧化氮（NO）生成和诱导型一氧化氮合酶（iNOS）mRNA表达的影响。实验结果表明，在用佛波酯PMA预处理这些细胞后，二氧化硅在体外以时间依赖性方式显著刺激THP-1细胞产生一氧化氮。一氧化氮合酶抑制剂N-单甲基-L-精氨酸（NMMA）和黄嘌呤氧化酶抑制剂别嘌呤醇均可部分抑制PMA预处理的THP-1细胞中二氧化硅诱导的NO生成。Northern印迹分析表明，在二氧化硅暴露2小时后，PMA预处理的THP-1细胞开始表达iNOS mRNA，并在8小时达到表达峰值。用内毒素处理这些细胞也产生了类似的效果。这些结果表明，二氧化硅是巨噬细胞中NO生成的有效诱导剂，其诱导组织损伤的能力可能部分归因于其引发巨噬细胞过度产生一氧化氮的能力。
