Alveolar type II cells: effect of silica.
NIOSH 1988 Sep; :1-40
The role of silica (14808607) in pulmonary disorders at the cellular level was investigated in rat lung. The effect of exposure to silica inhalation on two cytochrome-P450 dependent enzymes (ethoxycoumarin-deethylase and ethoxyphenoxazone-deethylase) in the lung microsomal fraction was studied in male Sprague-Dawley-rats. Exposure to silica had no statistically significant effect on the induction ratio for either activity. Silica exposure may have caused a diminished level of the constitutive enzyme activity in rat lung tissue. Cytochrome-P450 dependent enzymes in the isolated microsomal fraction from whole lung tissue and in isolated rat lung alveolar type-II cells were also studied. Lung microsomal benzyloxyphenoxazone-deethylase was shown to be a nonpolyaromatic hydrocarbon inducible, metyrapone sensitive activity whereas ethoxyphenoxazone-deethylase was a polycyclic aromatic hydrocarbon inducible, alpha-naphthoflavone sensitive form. The alveolar type- II cytochrome-P450 dependent system was tested for its sensitivity to a known purified macrophage secreted compound, platelet activating factor (PAF). PAF exposure enhanced ethoxyphenoxazone- deethylase activity in whole cells but not in microsomal or sonicated whole cell preparations. The effect of PAF may be mediated through a permeability mechanism or through the reversal of an inhibitory process. The authors conclude that a mediator secreted by activated macrophages can affect a critical detoxication mechanism in another cell type of the alveolar region.
NIOSH-Author; Lung-cells; Cell-function; Cell-damage; Silica-dusts; Inhalation-studies; Laboratory-animals; Pulmonary-function
NTIS Accession No.
Final Report, Division of Respiratory Disease Studies, NIOSH, 40 pages, 56 references