NITRIC OXIDE SYNTHESIS,NITROSOGLUTATHIONE FORMATION AND POSSIBLE GENERATION OF PEROXYNITRITE IN THE CULTURE OF ALVOLAR MACROPHAGES WITH ASBESTOS OR MAN-MADE MINERAL FIBERS.

石棉或人造矿物纤维培养的肺泡巨噬细胞中一氧化氮的合成、亚硝基谷胱甘肽的形成以及过氧亚硝酸盐的可能生成。

基本信息

批准号：
09670357
负责人：
IGUCHI Hiroshi
金额：
$ 1.98万
依托单位：
HYOGO COLLEGE OF MEDICINE (1998)Kyoto University (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

When cultured with chrysotile asbestos or man-made mineral fibers(MMMF), rat alveolar macrophages (AMs) concomitantly produced in a significant amount of nitric oxide(NO) and superoxide anion (O_2-), indicating a possible formation of peroxynitrite (ONOO-) and its decomposition to hydroxyl radical (・OH), which is very toxic to various cells and tissues. These findings strongly suggest that all of NO, O_2- , ONOO- and OH derived from decomposition of ONOO- are implicated in the development of asbestos- or MMMF-induced lung diseases. Moreover, such findings were also consistent with NO synthesis and histological pathologies observed in the previous studies of rat instilled asbestos into the trachea.NOsythesized by AMs cultured with asbestos or MMMF also readily reacts with thiol compounds, especially with reduced glutathione (GSH) in the cells to form nitrosocompounds such as nitrosoglutathione (GS-NO). As expected, GS-NO was detectable in the conditioned media from the culture of AMs with asbestos or MMMFS, but hardly detected in the cell layer. This finding indicates that GS-NO is released into extracellular space similarly to oxidized glutathione. The amount of GS-NO in the conditioned media from culture of AMs with asbestos or MMMFs was small and comparable to that from the control culture of AMs alone. However, AMs cultured with bacterial endotoxin, LPS remarkably enhanced NO synthesis to release a large amount of GS-NO in the conditioned media. Thus, mineral fibers added into the culture of AMs did not increase the amount of GS-NO.It therefore follows that as far as GSH synthesis systems of AMs are not affected in the culture with mineral fibers, intracellular GSH level is not significantly decreased.

When cultured with chrysotile asbestos or man-made mineral fibers(MMMF), rat alveolar macrophages (AMs) concomitantly produced in a significant amount of nitric oxide(NO) and superoxide anion (O_2-), indicating a possible formation of peroxynitrite (ONOO-) and its decomposition to hydroxyl radical (・OH), which is very toxic to various cells和组织。这些发现强烈表明，在石棉或MMMF诱导的肺部疾病的发展中暗示了所有NO，O_2-，ONOO-和OH。 Moreover, such findings were also consistent with NO synthesis and histological pathologies observed in the previous studies of rat instilled asbestos into the trachea.NOsythesized by AMs cultured with asbestos or MMMF also readily reacts with thiol compounds, especially with reduced glutathione (GSH) in the cells to form nitrosocompounds such as nitrosoglutathione (GS-NO).如预期的那样，在有石棉或MMMF的AM培养基中检测到了GS-NO，但在细胞层中几乎未检测到GS-NO。这一发现表明，GS-NO被释放到类似于氧化的谷胱甘肽的细胞外空间中。来自AMS或MMMFS培养的条件培养基中的GS-NO量很小，并且与单独的AMS的控制文化相当。然而，用细菌内毒素培养的AMS LPS明显增强没有合成，可以在条件培养基中释放大量的GS-NO。因此，将矿物纤维添加到AM的培养物中并没有增加GS-NO的量。因此，就矿物纤维的培养物中的GSH合成系统而言，AMS的GSH合成系统不会显着改善。