Effect of silica on nitric oxide (NO) production by rat alveolar macrophages.
Huffman-LJ; Judy-JD; Castranova-V
FASEB J 1994 Apr; 8(4):A150
In vivo exposure of rats to silica increases NO production by bronchoalveolar lavageable cells (BALC), a population of cells which includes alveolar macrophages (AMs). In the present study, we examined the in vitro effects of silica on NO production by rat AMs. BALC were obtained from normal male rats and cultured for 2 hrs. Non-adherent cells were then removed and the remaining AMs were exposed to test agents for 18-20 hrs. Media nitrate and nitrite concentrations were used to index NO production. Lipopolysaccharide (100 ng/ml) and rat interferon y (IFN; 10 U/ml) increased NO production and enhanced inducible NO synthase mRNA levels in cultured AMs. Treatment with silica (1-100 ug/ml) had no effect on basal NO levels. Furthermore, IFN-induced increases in NO were not altered by the simultaneous addition of silica (100 ug/ml) or by a 2 hr pretreatment with silica (1 ug/ml). To evaluate whether cell-to-cell interactions might be required for the induction of NO production during in vivo silica challenge, AMs (1 x 10-6) and non-adherent splenic lymphocytes (20 x 10-6) were cultured separately or together, with or without silica (100 ug/ml). The combination of these cell types resulted in a synergistic increase in NO above levels produced by each of these cell types alone. Furthermore, silica appeared to further enhance this effect. These data indicate that silica alone is not a sufficient stimulus to increase NO production by AMs and suggest that cell-to-cell interactions are important in NO generation by BALC during in vivo silica exposure.
Silicates; Silica-dusts; Pulmonary-system-disorders; Respiratory-irritants; Respiratory-system-disorders; Alveolar-cells; Lung-disorders; Lung-irritants; Lung-cells; Laboratory-animals; Animal-studies
The FASEB Journal. Experimental Biology '94, Anaheim, California, April 24-28, 1994