NIOSHTIC-2 Publications Search
Silica exposure induces arginase I expression in rat lung.
Poljakovic-M; Porter-DW; Kepka-Lenhart-D; Millecchia-L; Mercer-RR; Castranova-V; Morris-SM Jr.
Proc Am Thorac Soc 2005 May; 2(Abstracts):A818
Induction of arginase (ARG) in some inflammatory lung diseases (e.g., asthma) suggests that it may play a role in bronchoconstriction, fibrosis and airway remodeling by reducing substrate for NO synthesis and enhancing metabolism of arginine to proline and polyamines. Our objectives were to ascertain whether ARG induction is also a feature of silicosis and, if so, to identify the cells expressing type I ARG (ARG I) in rat lung following silica exposure. Sprague-Dawley rats received vehicle or 0.1, 1.0 or 5.0 mg silica/100 g body weight by intratracheal instillation. After 24h, bronchoalveolar lavage (BAL) was performed and markers of pulmonary inflammation, damage and alveolar macrophage (AM) activation were examined. ARG expression was examined by real-time PCR and activity assay. ARG I and iNOS were analyzed by immunohistochemistry. Markers of pulmonary inflammation , damage and AM activation and NO production were significantly increased at all silica doses tested. Silica caused 2- and 3-fold increases in ARG activity at 1 and 5 mg/100 g doses, respectively. ARG I, but not type II ARG, mRNA increased in a similar pattern. In control lungs, ARG I immunoreactivity was observed in AM only. In silica-treated lungs, ARG I immunoreactivity was observed in alveolar type II epithelial cells and in clustered AM, while iNOS was seen only in some AM. ARG activity in AM isolated by BAL also increased significantly after silica treatment. The pattern of ARG I induction is similar to that seen in other models of acute lung disease, suggesting that increases in ARG I may play a common role in the pathology of some lung diseases. Studies to evaluate the impact of inhibiting ARG activity in lung disease are warranted.
Laboratory-animals; Animals; Animal-studies; Silica-dusts; Silicates; Lung-disease; Bronchial-asthma; Silicosis; Exposure-levels; Exposure-assessment; Pulmonary-system-disorders; Respiratory-system-disorders
Abstract; Conference/Symposia Proceedings
Issue of Publication
Proceedings of the American Thoracic Society