title: Ferritin expression after in vitro exposures of human alveolar macrophages to silica is iron-dependent.
abstract: The increased availability of catalytically active iron after silica exposure can present an oxidative injury to a living system. Sequestration of reactive iron would, therefore, confer a protective effect. The intracellular storage of iron by ferritin within macrophages can limit the potential for radical generation and cellular injury resulting from exposure to a metal chelate. We tested the hypothesis that in vitro exposure of human alveolar macrophages to silica increases the expression of ferritin through a posttranscriptional mechanism. Exposure of 1.0 x 10(6) macrophages to 100 microg/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 mixtures inhibited increases in ferritin after silica. To test for a posttranscriptional regulation of ferritin protein expression, cells were incubated with acid-washed particles, silica with complexed zinc cation, and silica with complexed iron cation. L-ferritin protein concentrations were increased in both cell supernatants and lysates after 4 h of exposure to silica with complexed iron cation. There were no increases in L-ferritin after incubations with acid-washed particles or silica with complexed zinc cation. There were no significant differences in levels of L-ferritin cDNA between any of the exposures, suggesting a posttranscriptional control of ferritin expression.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: J D
authors.initials: JD
authors.lastname: Carter
authors.forename: J M
authors.initials: JM
authors.lastname: Samet
authors.forename: J
authors.initials: J
authors.lastname: Quay
authors.forename: I A
authors.initials: IA
authors.lastname: Wortman
authors.forename: J H
authors.initials: JH
authors.lastname: Richards
authors.forename: T P
authors.initials: TP
authors.lastname: Kennedy
authors.forename: R B
authors.initials: RB
authors.lastname: Devlin
mesh_terms: D002478:Cells, Cultured; D005293:Ferritins / Q000096:biosynthesis*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D012822:Silicon Dioxide / Q000494:pharmacology*
chemical_list: D012822:Silicon Dioxide; D005293:Ferritins; D007501:Iron