METAL-DEPENDENT EXPRESSION OF FERRITIN AND LACTOFERRIN BY RESPIRATORYEPITHELIAL-CELLS

Increased availability of catalytically active metal has been associat ed with an oxidative injury. The sequestration of transition metals wi thin intracellular ferritin confers an antioxidant function to this pr otein. 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 epithel ial cells increase the production of lactoferrin and ferritin to bind, transport, and store this metal with their coordination sites fully c omplexed. Residual oil fly ash is an emission source air pollution par ticle with biological effects that, both in vitro and in vivo, corresp ond with its metal content. Cell cultures were exposed to 0-200 mu g/m l of oil fly ash for 2 and 24 h. Concentrations of ferritin and lactof errin mRNA were estimated by reverse transcription-polymerase chain re action, and concentrations of ferritin and lactoferrin proteins were m easured in parallel, mRNA for ferritin did not change with exposure to oil fly ash. However, ferritin protein concentrations increased. Alth ough mRNA for transferrin receptor decreased, mRNA for lactoferrin inc reased after incubation with the particle. Similar to changes in mRNA, transferrin concentration decreased, whereas that of lactoferrin incr eased. Deferoxamine, a metal chelator, inhibited these responses, and exposure of the cells to vanadium compounds alone reproduced elevation s in lactoferrin mRNA. We conclude that increases in ferritin and lact oferrin expression can be metal dependent. This response can function to diminish the oxidative stress a metal chelate presents to a living system.