Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells

The factors that determine whether an exogenous mineral particle will be taken up by tracheobronchial epithelial cells are unclear. We have previously proposed that active oxygen species play a role in this process, most likely through iron-catalyzed formation of hydroxyl radical and subsequent lipid peroxidation of cell membranes. To further examine this hypothesis, we prepared rat tracheal explant cultures and exposed them for 1 h to suspensions of amosite asbestos or titanium dioxide (rutile) that had been preincubated with varying concentrations of a mixture of ferrous and ferric chloride. Explants were then maintained in organ culture in air/CO2 for 1 wk to allow particle or fiber uptake to occur. Particles or fibers in the tracheal epithelium were determined by light microscopic morphometry. Similarly treated explants were assayed for malondialdehyde as a measure of lipid peroxidation in the epithelial cells. Asbestos fibers without added iron caused lipid peroxidation, but this was not true of titanium dioxide particles. For both types of dust, increasing adsorbed iron concentrations were associated with increasing particle uptake and increasing lipid peroxidation. These observations suggest that cationic iron may play a major role in particle uptake by tracheobronchial epithelia, and that particle uptake is also related to iron-mediated lipid peroxidation.