PHAGOCYTE-GENERATED SUPEROXIDE REDUCES FE3+ TO DISPLACE IT FROM THE SURFACE OF ASBESTOS

Injury after exposure to mineral oxide dusts is considered to be media ted by free radical generation. In vitro production of hydroxyl radica l by a fibrous silicate increases with the [Fe3+] complexed to the dus t surface. The study hypothesis tested was that extracellular fluids a nd phagocytic cells can decrease concentrations of iron complexed to t he surface of a fibrous silicate by employing host chelators and reduc tants. 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 e xposed 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) cel ls/ml) or 10.0 ml rat neutrophils (1.0 X 10(7) cells/ml) decreased con centrations of surface iron, In vivo exposures of asbestos contained i n chambers allowing or precluding inflammatory cell entry revealed tha t the influx of phagocytes was associated with greater decreases in su rface [Fe3+]. The body chelators transferrin and lactoferrin were unab le to extract the metal from fiber surface in vitro. However, superoxi de generated by phagocytes did displace the iron from the crocidolite surface. We conclude that extracellular fluids and phagocytic cells ha ve a capacity to diminish [Fe3+] complexed to the surface of asbestos and therefore decrease the potential for oxidative stress and injury t o a living system after exposure to these dusts. Rather than a direct reaction with a chelator either resident in lining fluid or released b y phagocytes, this effect is likely the result of Fe3+ reduction by re ducing agents in the fluids and by superoxide generated by phagocytic cells. (C) 1994 Academic Press, Inc.