Poljakovic-M; Porter-DW; Millecchia-L; Kepka-Lenhart-D; Beighley-C; Wolfarth-MG; Castranova-V; Morris-SM Jr.
J Toxicol Environ Health, A 2007 Jan; 70(2):118-127
Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase were elucidated in lungs of Sprague-Dawley rats 24 h following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time polymerase chain reaction (PCR), and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced two- and three-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100 g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no inducible nitric oxide synthase (iNOS) immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica.
Silica-dusts; Pulmonary-system-disorders; Respiratory-system-disorders; Lung-disease; Animal-studies; Dose-response; Immunochemistry; Cellular-reactions; Biomarkers
Sidney M. Morris Jr., Ph.D., Department of Molecular Genetics and Biochemistry, W1255 Biomedical Science Tower, University of Pittsburgh School of Medicine. Pittsburgh, PA 15261
7631-86-9; 14808-60-7; 10102-43-9
Journal of Toxicology and Environmental Health, Part A: Current Issues