Ferritin expression after in vitro exposures of human alveolar macrophages to silica is iron-dependent.
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.
Ghio
A J
AJ
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Carter
J D
JD
Samet
J M
JM
Quay
J
J
Wortman
I A
IA
Richards
J H
JH
Kennedy
T P
TP
Devlin
R B
RB
D002478:Cells, Cultured; D005293:Ferritins / Q000096:biosynthesis*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D012822:Silicon Dioxide / Q000494:pharmacology*
D012822:Silicon Dioxide; D005293:Ferritins; D007501:Iron