Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases.

Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure to asbestos caused rat AM to exhibit high production of transforming growth factor-beta (TGF-ß) with prolonged survival in the absence of other cells, not simultaneously with the apoptosis caused by asbestos. The NK cell line showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, and primary NK cells in culture with asbestos and peripheral blood NK cells in mesothelioma shared a decrease in expression of NKp46, a representative activating receptor. The AM finding indicates that AM contribute to asbestosis by playing a direct role in the fibrogenic response, as well as the inflammatory response. The response of NK cells indicates that exposure to asbestos has an immune-suppressive effect, as well as a tumorigenic effect. Our studies therefore reveal novel effects of asbestos exposure on AM and tumor immunity, which may represent valuable information for construction of a strategy for prevention and cure of asbestosis and malignant mesothelioma.

Comparison and verification of BSE surveillance in USA and Japan.

OBJECTIVE: The objectives of this study are to (1) compare the BSE surveillance systems of Japan and the United States (US), and to (2) validate the US enhanced BSE Surveillance program. METHODS: This study compares the BSE surveillance systems in Japan and the US, specifically focusing on the procedures of initial test, diagnosis and confirmation. The study further examines the validity of statistical conclusions made in the US enhanced surveillance program based on the data collected from the BSE inspection performed by the Ministry of Health, Labor and Welfare of Japan (MHLW) and the Ministry of Agriculture, Forestry and Fisheries of Japan (MAFF) between October 18,2001 and July 31, 2004. The inspection targeted all slaughtered healthy and high risk cattle. RESULTS: The US enhanced surveillance program assumes no BSE occurrence in the normal adult cattle population and thus its inspection focuses only on high risk cattle. The BSE inspection performed in Japan, however, revealed that 0.00022% of the normal adult cattle were BSE-infected using the US criteria. Assuming that the same ratio of cattle was BSE-infected in the US, the Japan finding indicates that approximately 30% of the US slaughtered normal cattle population aged 30 months and over needs to be tested to satisfy the statistical condition used by the US (i.e., 99% confidence level). On the other hand, in order for Japan to perform the surveillance with a 99% confidence level (the statistical condition used by US), Japan needs inspect: (1) 60,539 high risk cattle (i.e., 60% of 100,583 high risk cattle); (2) 78% of normal adult cattle aged 30 months and over (1,088,589/1,387,522) and (3) 90% of normal cattle aged 30 months or less (1,845,138/2,050,154). CONCLUSION: The US enhanced surveillance program launched in July 2004 is based on the premise that no BSE occurs in normal adult cattle population. In Japan, however, BSE cases satisfying the US criteria have been found among the normal adult cattle. This fact suggests that the US needs to consider inspections targeting the normal adult cattle. This fact suggests that the US needs to consider inspections targeting the normal adult cattle in the future. At the same time, for more efficient surveillance, Japan may need to consider BSE inspections targeting the high risk cattle population with a higher confidence level and normal adult cattle with a lower confidence level.

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes.

The purpose of this study was to investigate the effects of pneumoconiogenic particles, such as asbestos, on nitrosothiol formation in macrophages. In addition, the effects of man-made mineral fibers (MMMFs) were also evaluated, because they have come into heavy use as substitutes for asbestos. RAW264.7 cells and J774 cells of murine macrophage cell lines were cultured with chrysotile B (CH) asbestos, crocidolite (CR) asbestos, or MMMFs comprised of glass wool (GW), rock wool (RW), or ceramic (RF1). All of these fibers significantly increased nitric oxide (NO) production in the culture with macrophages. Chrysotile B, CR, and GW significantly decreased the level of reduced glutathione (GSH) in RAW264.7 cells. S-nitrosothiol (RS-NO) formation was increased by both types of cells on exposure to every fiber. A large portion of this increased RS-NO may be in the form of S-nitrosoglutathione (GS-NO), because GSH is the most abundant thiol substance in the cell. Both CH and GW significantly increased superoxide anion in the media cultured of RAW264.7 cells. These results indicate that macrophages exposed to asbestos or MMMFs are subject to oxidative stress, not only through the generation of reactive oxygen and nitrogen species, but also through decreases in the level of the cellular antioxidant, GSH, by GS-NO formation. The increase of RS-NO in macrophages exposed to asbestos or MMMFs may deserve more attention as the indicator of continuous oxidative stress by NO on cells and tissues, which causes inflammation and involves the development of asbestos-induced diseases.