Phagocyte-generated superoxide reduces Fe3+ to displace it from the surface of asbestos.
Injury after exposure to mineral oxide dusts is considered to be mediated by free radical generation. In vitro production of hydroxyl radical by a fibrous silicate increases with the [Fe3+] complexed to the dust surface. The study hypothesis tested was that extracellular fluids and phagocytic cells can decrease concentrations of iron complexed to the surface of a fibrous silicate by employing host chelators and reductants. Such a depletion of surface [Fe3+] would predict decrements in both oxidant generation and the resultant injury after inhalation and instillation of these mineral oxides. Crocidolite (2.0 mg) which was exposed to either 5.0 ml rat plasma or 10.0 ml rat lavage fluid for 1 h had diminished surface [Fe3+]. Similarly, incubations of crocidolite (2.0 mg) with either 10.0 ml rat alveolar macrophages (1.0 x 10(6) cells/ml) or 10.0 ml rat neutrophils (1.0 x 10(7) cells/ml) decreased concentrations of surface iron. In vivo exposures of asbestos contained in chambers allowing or precluding inflammatory cell entry revealed that the influx of phagocytes was associated with greater decreases in surface [Fe3+]. The body chelators transferrin and lactoferrin were unable to extract the metal from fiber surface in vitro. However, superoxide generated by phagocytes did displace the iron from the crocidolite surface. We conclude that extracellular fluids and phagocytic cells have a capacity to diminish [Fe3+] complexed to the surface of asbestos and therefore decrease the potential for oxidative stress and injury to a living system after exposure to these dusts.(ABSTRACT TRUNCATED AT 250 WORDS)
Ghio, AJ; Stonehuerner, J; Steele, MP; Crumbliss, AL
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