FERRITIN EXPRESSION AFTER IN-VITRO EXPOSURES OF HUMAN ALVEOLAR MACROPHAGES TO SILICA IS IRON-DEPENDENT

The increased availability of catalytically active iron after silica e xposure can present an oxidative injury to a living system. Sequestrat ion of reactive iron would, therefore, confer a protective effect. The intracellular storage of iron by ferritin within macrophages can limi t the potential for radical generation and cellular injury resulting f rom exposure to a metal chelate. We tested the hypothesis that in vitr o exposure of human alveolar macrophages to silica increases the expre ssion of ferritin through a posttranscriptional mechanism. Exposure of 1.0 x 10(6) macrophages to 100 mu g/ml silica for 4 h increased light -subunit (L)-ferritin protein concentrations in both cell supernatants and lysates. Inclusion of 1.0 mM deferoxamine in the reaction mixture s inhibited increases in ferritin after silica. To test for a posttran scriptional regulation of ferritin protein expression, cells were incu bated with acid-washed particles, silica with complexed zinc cation, a nd silica with complexed iron cation. L-ferritin protein concentration s were increased in both cell supernatants and lysates after 4 h of ex posure to silica with complexed iron cation. There were no increases i n L-ferritin after incubations with acid-washed particles or silica wi th complexed zinc cation. There were no significant differences in lev els of L-ferritin cDNA between any of the exposures, suggesting a post transcriptional control of ferritin expression.