Englen M D, Taylor S M, Laegreid W W, Silflow R M, Leid R W
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman 99164-7040.
Am J Respir Cell Mol Biol. 1992 May;6(5):527-34. doi: 10.1165/ajrcmb/6.5.527.
Modification of the silica surface has been shown to reduce its cytotoxicity in vitro and its fibrogenic activity in vivo. We have shown silica to be a potent stimulator of arachidonic acid (AA) metabolism in bovine alveolar macrophages (BAM). To determine the effect of surface-modified silica on AA metabolism in BAM, we exposed BAM in vitro to silica treated with aluminum lactate or polyvinylpyridine-N-oxide (PVPNO). BAM were prelabeled with [3H]AA and incubated with 3 and 5 mg of silica. Unmodified silica at these doses elicited maximal AA metabolite release from BAM. AA metabolites were analyzed by high performance liquid chromatography. Lactate dehydrogenase release was quantitated to determine the cytotoxicity of treated and untreated silica on BAM. Treating silica with aluminum lactate or PVPNO significantly (P less than or equal to 0.05) reduced 5-lipoxygenase metabolite release and significantly (P less than or equal to 0.05) increased cyclooxygenase metabolite release. These changes in AA metabolite release were accompanied by a significant (P less than or equal to 0.05) reduction in the cytotoxicities of the treated silicas compared with untreated silica. Our results suggest that the reduced inflammatory and fibrogenic activity of surface-modified silica may in part be due to reduced AA metabolite release from exposed macrophages.
二氧化硅表面的修饰已被证明可降低其体外细胞毒性和体内纤维生成活性。我们已表明二氧化硅是牛肺泡巨噬细胞（BAM）中花生四烯酸（AA）代谢的有效刺激物。为了确定表面修饰的二氧化硅对BAM中AA代谢的影响，我们在体外将BAM暴露于用乳酸铝或聚乙烯吡啶-N-氧化物（PVPNO）处理的二氧化硅。BAM预先用[3H]AA标记，并与3毫克和5毫克二氧化硅一起孵育。这些剂量的未修饰二氧化硅引起BAM中AA代谢产物的最大释放。通过高效液相色谱分析AA代谢产物。定量乳酸脱氢酶释放以确定处理过的和未处理的二氧化硅对BAM的细胞毒性。用乳酸铝或PVPNO处理二氧化硅可显著（P≤0.05）减少5-脂氧合酶代谢产物的释放，并显著（P≤0.05）增加环氧化酶代谢产物的释放。与未处理的二氧化硅相比，这些AA代谢产物释放的变化伴随着处理过的二氧化硅细胞毒性的显著（P≤0.05）降低。我们的结果表明，表面修饰的二氧化硅炎症和纤维生成活性降低可能部分归因于暴露的巨噬细胞中AA代谢产物释放减少。
