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石棉对大鼠肺部以及大鼠肺泡巨噬细胞和II型肺细胞原代培养的影响。

The effect of stone-wool on rat lungs and on the primary culture of rat alveolar macrophages and type II pneumocytes.

作者信息

Tátrai Erzsébet, Brozik Márta, Drahos Agnes, Kováciková Zuzana, Six Eva, Csík Márta, Dám Annamária

机构信息

Fodor József National Center for Public Health, Budapest, Hungary.

出版信息

J Appl Toxicol. 2006 Jan-Feb;26(1):16-24. doi: 10.1002/jat.1099.

Abstract

The effect of stone-wool has been studied in both in vivo long term sequential and in vitro methods in male Sprague-Dawley rats. Stone-wool was administered by single intratracheal instillation and the lungs were examined after 1, 3 and 6 months of exposure by morphological methods. UICC crocidolite was applied as a positive control. In addition, the effects of both fibres were examined in primary cultures of alveolar macrophages (AM) and type II pneumocytes (T2) by morphological, biochemical and immunological methods. By the end of 6 months stone-wool induced moderate pulmonary interstitial inflammation and fibrosis without progression, whereas crocidolite induced progressive interstitial inflammation and fibrosis as a function of time. Although stone-wool inhibited phagocytosis, it did not induce serious membrane damage to the cells examined and did not destroy their ultrastructure. It significantly reduced the activity of Cu,Zn/superoxide dismutase (SOD) and alkaline phosphatase (AP) in alveolar macrophages and significantly decreased the activity of AP and gamma-glutamyl transpeptidase (GGT) in type II pneumocytes. Crocidolite, on the other hand, decreased the activity of all enzymes (glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Rd) of glutathione metabolism as well as alkaline phosphatase in alveolar macrophages. It decreased the activity of all enzymes in type II pneumocytes, except for Cu,Zn/SOD. On exposure to stone-wool, the production of inflammatory proteins, macrophage chemoattractant protein-1 (MCP-1) and macrophage inhibitory protein-1alpha (MIP-1alpha) increased in both cultured cells but did not reach the level induced by crocidolite. Our results suggested that stone-wool is less toxic than crocidolite. Whether it is carcinogenic or not, is still an open question.

摘要

在雄性斯普拉格-道利大鼠中,已通过体内长期序贯法和体外法研究了石棉的影响。通过单次气管内滴注给予石棉,并在暴露1、3和6个月后通过形态学方法检查肺部。将国际癌症研究机构(UICC)的青石棉用作阳性对照。此外,通过形态学、生化和免疫学方法在肺泡巨噬细胞(AM)和II型肺细胞(T2)的原代培养物中研究了两种纤维的影响。在6个月末,石棉引起中度肺间质炎症和纤维化且无进展,而青石棉随时间推移引起进行性间质炎症和纤维化。尽管石棉抑制吞噬作用,但它并未对所检查的细胞造成严重的膜损伤,也未破坏其超微结构。它显著降低了肺泡巨噬细胞中铜锌超氧化物歧化酶(SOD)和碱性磷酸酶(AP)的活性,并显著降低了II型肺细胞中AP和γ-谷氨酰转肽酶(GGT)的活性。另一方面,青石棉降低了肺泡巨噬细胞中谷胱甘肽代谢的所有酶(谷胱甘肽过氧化物酶,GSH-Px;谷胱甘肽还原酶,GSH-Rd)以及碱性磷酸酶的活性。它降低了II型肺细胞中除铜锌超氧化物歧化酶之外的所有酶的活性。暴露于石棉时,两种培养细胞中炎性蛋白、巨噬细胞趋化蛋白-1(MCP-1)和巨噬细胞抑制蛋白-1α(MIP-1α)的产生均增加,但未达到青石棉诱导的水平。我们的结果表明,石棉的毒性低于青石棉。它是否具有致癌性仍是一个悬而未决的问题。

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