Intratracheal instillation of silica up-regulates inducible nitric oxide synthase gene expression and increases nitric oxide production in alveolar macrophages and neutrophils.
Blackford-JA Jr.; Antonini-JM; Castranova-V; Dey-RD
Am J Respir Cell Mol Biol 1994 Oct; 11(4):426-431
The effect of silica (14808607) installation on inducible nitric- oxide synthase (iNOS) gene expression and nitric-oxide production was examined in rat alveolar macrophages and neutrophils. Sprague- Dawley-rats were instilled with silica, saline, or bacterial lipopolysaccharide (LPS). After 24 hours, animals were sacrificed for isolation of bronchoalveolar lavage cells (BALC) and lung tissue. Northern blot analysis revealed that BALC iNOS messenger RNA (mRNA) steady state levels were increased three fold by silica and seven fold by LPS. Partially enriched fractions of either alveolar macrophages or leukocytes from silica treated rats exhibited significantly elevated iNOS mRNA in Northern blot analysis. Additionally, iNOS dependent chemiluminescence in alveolar macrophages was increased 36 fold by silica and 89 fold by LPS. Differential counts revealed no treatment induced differences in the alveolar macrophage population; the red blood cell population, in contrast, was increased 30 fold by silica and 23 fold by LPS. Total leukocytes were increased 58 fold by silica and 274 fold by LPS. The authors conclude that these findings strongly support the hypothesis that silica upregulates iNOS mRNA and increases nitric-oxide production in alveolar macrophages; the subsequent formation of peroxynitrite by combination of nitric-oxide with superoxide may play a role in the development of silica induced lung damage.
NIOSH-Author; Pulmonary-system; Genotoxic-effects; Laboratory-animals; Silica-dusts; Cytotoxicity; Cell-damage; Lung-cells; Lung-disorders; Free-radical-generation; Alveolar-cells
American Journal of Respiratory Cell and Molecular Biology