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

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.

Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

“…The results after exposure to stone wool were different: in TII cells the production of MCP-1 was enhanced at all concentrations, MIP-1Ǐ at doses of 5 and 10 μg.ml -1 ; in AM the production of both cytokines was statistically significantly enhanced after doses of 5 and 10 μg.ml -1 . Crocidolite evoked statistically significant dose dependent enhancement of the production of MCP-1 in AM, for MIP-1Ǐ and both cytokines in TII at doses of 5 and 10 μg.ml -1 in all cases (Tátrai et al, 2004;2006a;2006b). Comparing the results from different fibers on 2 various primary cell types the following differences are clearly seen: crocidolite (asbestos) evoked the greatest changes, both morphologically and functionally.…”

“…Wollastonite caused a decreased reaction in the membranes only at the highest dose. After exposure to the lowest dose of crocidolite the membranes of both cell types were fragmented irregularly and frustrated phagocytosis could be found in AM (Tátrai et al, 2004;2006a;2006b).…”

“…AM cells phagocyted RCF fibers without injuries of cell organelles, intact organelles remained also after exposure to stone wool. In both cell types crocidolite evoked severe damage in the organelles and necrobiosis of whole cells (Tátrai et al, 2004;2006a;2006b). …”

Asbestos induces doxorubicin resistance in MM98 mesothelioma cellsviaHIF-1α

“…Moreover, following the phagocytosis of asbestos fibres, macrophages may produce ROS by activating nicotinamide adenine dinucleotide phosphate oxidase [32]. Asbestos may also evoke oxidative stress via other mechanisms, such as the inhibition of the pentose phosphate pathway [35], the decrease of several antioxidant enzymes (glutathione peroxidase, glutathione reductase and catalase) [36,37] and the enhanced leakage of reduced glutathione [38]. Asbestos-induced oxidative stress may directly damage DNA, impair the DNA repairing systems and activate some redox-sensitive transcription factors, such as nuclear factor-kB [1] and HIF-1a [30].…”

Macrophage Culture as a Suitable Paradigm for Evaluation of Synthetic Vitreous Fibers

“…Respiratory burst can be assessed by measuring the activity of enzymes involved in ROS detoxification, like glutathione reductase and glutathione peroxidase (GSH) [69], superoxide dismutase (SOD) [36,70,71], and inducible nitric oxide synthase (iNOS) [71][72][73] and its product, nitric oxide (NO) ( Table 2). Compared to asbestos fibers, rock wool fiber did not seem to be toxic toward enzymes of glutathione metabolism in primary cultured rat AMs [71].…”