Role of Nitric Oxide Radicals in Asbestos-Induced Injury

Abstract

It is well recognized that inhalation of asbestos fibers is linked to the causation of a variety of clinical disorders including interstitial pulmonary fibrosis, parietal pleural plaques, bronchogenic carcinoma and diffuse malignant mesothelioma of the pleura and peritoneum (Kagan, 1985; Mossman and Gee, 1989). Although the pathogenesis of these diseases has not been elucidated fully, there is evidence that alveolar macrophages (AM) play a pivotal role in mediating asbestos-related injury. Thus, studies in asbestosexposed rodents and in asbestos workers have shown that AM are recruited to the sites of deposition of inhaled asbestos fibers (Kagan, 1988; Rom et al., 1991). It has also been demonstrated that asbestos fibres can activate AM to secrete a diverse group of inflammatory mediators including cytokine growth factors, chemoattractants and arachidonic acid metabolites (Kagan, 1988; Rom, et al., 1991). Several studies also have demonstrated that the in vitro phagocytic uptake of asbestos fibers can generate a variety of reactive oxygen species (ROS) such as the superoxide anion \((O_2^{* - })\), the hydroxyl radical (OH*) and hydrogen peroxide (Shull, et al., 1992; Mossman, et al., 1986). It also has been reported that scavengers of oxygen free radicals, such as superoxide dismutase (SOD) and catalase, may ameliorate the injurious effects of asbestos exposure (Mossman, et al,. 1986; Mossman, et al,. 1990). These studies are predicated on \((O_2^{* - })\)-driven, iron-catalyzed, Fenton-Haber-Weiss reactions which generate the OH* radical (Grisham, 1992), and suggest that ROS may have an important role in the pathobiology of asbestos-related disease.