Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica

Abstract

In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-kappa B activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m(3) silica, 6 h/day, 5 days/wk) for 116 days. We report time-dependent changes in 1) activation of alveolar macrophages and concomitant production of NO and ROS, 2) immunohistochemical localization of inducible NO synthase and the NO-induced damage product nitrotyrosine, 3) bronchoalveolar lavage fluid NO(x) and superoxide dismutase concentrations, and 4) lung lipid peroxidation levels. The major observations made in this study are as follows: 1) NO and ROS production and resultant damage increased during silica exposure, and 2) the sites of inducible NO synthase activation and NO-mediated damage are associated anatomically with pathological lesions in the lungs.

Cell- and Isoform-Specific Increases in Arginase Expression in Acute Silica-Induced Pulmonary Inflammation

“…The arginase Ipositive AMs were mainly localized to individual alveoli ( Figure 5A). No arginase I immunoreactivity was observed in alveolar type II epithelial cells (identified by immunostaining with antibody to pro-surfactant protein C; data not shown) nor were any iNOSpositive cells detected in saline-treated lungs ( Figure 5A), consistent with previous reports (Blackford et al, 1994;Blackford et al, 1997;Porter et al, 2002b;Srivastava et al, 2002).…”

“…Alveolar macrophage chemiluminescence was determined as described previously (Porter et al, 2002b). Briefly, resting AM chemiluminescence was determined by incubating 1.0 × 10 6 AM/ml at 37° C for 20 min, followed by the addition of luminol and the measurement of chemiluminescence.…”

“…However, the precise mechanisms underlying many of the pathophysiologic changes remain unknown. Many studies of the pulmonary toxicity of silica focussed on the role of nitric oxide (NO) because of the greatly increased expression of inducible NO synthase (iNOS) and NO production in lung following exposure to silica (Blackford et al, 1994;Porter et al, 2002b;Srivastava et al, 2002;Zeidler et al, 2004;Zeidler et al, 2003). However, the recent discoveries of increased arginase expression in asthma (Meurs et al, 2002;Zimmermann et al, 2003), bleomycin-induced pulmonary fibrosis (Endo et al, 2003), and hyperoxic lung injury (Que et al, 1998) raised the possibility that changes in arginase expression may occur also in silicosis and thus play roles in the pathophysiology of this disease.…”

Adverse effects of inhaled sand dust particles on the respiratory organs of sheep and goats exposed to severe sand storms in Mongolia

“…Experimental chronic www.fhc.viamedica.pl exposure to crystalline silica (SiO 2 ) reportedly causes granuloma formation [11][12][13][14][15] and/or fibrosis [16] in rats. In addition, granulomatous inflammation, characterized by the accumulation of epithelioid macrophages containing crystalline silica particles, in the tracheobronchial lymph nodes, has been reported in rats exposed to crystalline silica [12,17,18]. Silica is the major mineralogical component of ASD [19].…”

Immunological Effects of Silica and Related Dysregulation of Autoimmunity

“…As a consequence, the induction of cellular and tissue damages occur due to the production of ROS and RNS and the apoptosis of alveolar macrophages. Various cytokines/chemokines such as IL-1 ，tumor necrosis factor (TNF)-, macrophage inflammatory protein (MIP)-1/2, monocyte-chemoattractant protein-1 (MCP-1) and IL-8 are produced that cause chronic inflammation and proliferation of collagenic fibers (Barrett, 1999;Hamilton, 2008;Hubbard, 2001;Porter, 2002). Silica particles are released from alveolar macrophages and the similar cellular reactions described above by newly-recognizing nearby macrophages will be repeated.…”