Metal-dependent expression of ferritin and lactoferrin by respiratory epithelial cells.
Increased availability of catalytically active metal has been associated with an oxidative injury. The sequestration of transition metals within intracellular ferritin confers an antioxidant function to this protein. Such storage by ferritin requires that the metal be transported across a cell membrane. We tested the hypothesis that, in response to in vitro exposures to catalytically active metal, respiratory epithelial cells increase the production of lactoferrin and ferritin to bind, transport, and store this metal with their coordination sites fully complexed. Residual oil fly ash is an emission source air pollution particle with biological effects that, both in vitro and in vivo, correspond with its metal content. Cell cultures were exposed to 0-200 micrograms/ml of oil fly ash for 2 and 24 h. Concentrations of ferritin and lactoferrin mRNA were estimated by reverse transcription-polymerase chain reaction, and concentrations of ferritin and lactoferrin proteins were measured in parallel. mRNA for ferritin did not change with exposure to oil fly ash. However, ferritin protein concentrations increased. Although mRNA for transferrin receptor decreased, mRNA for lactoferrin increased after incubation with the particle. Similar to changes in mRNA, transferrin concentration decreased, whereas that of lactoferrin increased. Deferoxamine, a metal chelator, inhibited these responses, and exposure of the cells to vanadium compounds alone reproduced elevations in lactoferrin mRNA. We conclude that increases in ferritin and lactoferrin expression can be metal dependent. This response can function to diminish the oxidative stress a metal chelate presents to a living system.
Ghio
A J
AJ
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park 27711, USA.
Carter
J D
JD
Samet
J M
JM
Reed
W
W
Quay
J
J
Dailey
L A
LA
Richards
J H
JH
Devlin
R B
RB
D000393:Air Pollutants / Q000737:chemistry / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism*; D008670:Metals / Q000032:analysis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics; D014639:Vanadium / Q000494:pharmacology
D000393:Air Pollutants; D008670:Metals; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014639:Vanadium; D005293:Ferritins; D007781:Lactoferrin