Marks-Konczalik J, Gillissen A, Jaworska M, Löseke S, Voss B, Fisseler-Eckhoff A, Schmitz I, Schultze-Werninghaus G
Department of Internal Medicine, University Hospital Bergmannsheil, Bochum, Germany.
Lung. 1998;176(3):165-80. doi: 10.1007/pl00007600.
Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.
超氧化物歧化酶在肺部抵御纤维性粉尘（如青石棉纤维）的促氧化作用中发挥着重要的保护作用。尤其青石棉，但其他石棉纤维也已知会诱导细胞抗氧化防御。尽管岩棉这种由岩石制成的人造纤维被广泛用于绝缘目的，但其对支气管上皮细胞中超氧化物歧化酶的影响尚未得到研究。因此，本研究的目的是确定人支气管上皮细胞（BEAS 2B）是否会通过诱导MnSOD mRNA和提高MnSOD活性水平来对岩棉纤维（115 - 4实验性岩棉纤维）产生反应。将结果与暴露于二氧化硅（α - 石英：DQ12；SiO₂）和国际癌症研究机构（UICC）青石棉（所有粉尘浓度：0、2、5、10、25、50微克/平方厘米 = 0、2.4、6、12、30、60微克/毫升；暴露24小时）的BEAS 2B细胞作为对照纤维进行比较。扫描电子显微镜证实了在所有实验条件下粉尘与细胞的紧密接触。在暴露于2微克/平方厘米的所有三种粉尘的BEAS 2B细胞中，极低的MnSOD mRNA基线水平显著升高（p < 0.001）。然而，在> 25微克/平方厘米时，暴露于二氧化硅和青石棉而非岩棉的细胞中MnSOD mRNA水平下降。观察到MnSOD活性有轻微（无显著性）增加，在较高粉尘（> 5微克/平方厘米）浓度下下降。这些结果表明：（1）与青石棉和二氧化硅一样，岩棉可加速支气管上皮细胞中MnSOD基因的表达；（2）MnSOD mRNA水平的增加并未伴随着MnSOD活性的升高；（3）与岩棉相反，高浓度（≥25微克/平方厘米）的青石棉和二氧化硅会降低MnSOD活性和MnSOD mRNA水平。由于氧化剂（H₂O₂）和青石棉纤维已被证明会降低SOD活性，活性MnSOD蛋白的缺乏可能是由翻译后水平的失活引起的。此外，MnSOD mRNA和MnSOD活性水平的下降与细胞毒性的增加相吻合。总之，已证明岩棉可诱导MnSOD基因表达，可能是由于其在支气管上皮细胞中的促氧化作用。与青石棉和二氧化硅相反，在本实验条件下岩棉纤维没有细胞毒性。
