title: Ferrous iron release from transferrin by human neutrophil-derived superoxide anion: effect of pH and iron saturation.
abstract: The ability of superoxide anion (O2-) from stimulated human neutrophils (PMNs) to release ferrous iron (Fe2+) from transferrin was assessed. At pH 7.4, unstimulated PMNs released minimal amounts of O2- and failed to facilitate the release of Fe2+ from holosaturated transferrin. In contrast, incubation of phorbol myristate acetate (PMA)-stimulated PMNs with holosaturated transferrin at pH 7.4 enhanced the release of Fe2+ from transferrin eightfold in association with marked generation of O2-. The release of Fe2+ was inhibited by addition of superoxide dismutase (SOD), indicating that the release of Fe2+ was dependent on PMN-derived extracellular O2-. In contrast, at physiologic pH (7.4), incubation of transferrin at physiological levels of iron saturation (e.g. 32%) with unstimulated or PMA stimulated PMNs failed to facilitate the release of Fe2+. The effect of decreasing the pH on the release of Fe2+ from transferrin by PMN-derived O2- was determined. Decreasing the pH greatly facilitated the release of Fe2+ from both holosaturated transferrin and from transferrin at physiological levels of iron saturation by PMN-derived O2-. Release of Fe2+ occurred despite a decrease in the amount of extracellular O2- generated by PMNs in an acidic environment. These results suggest that transferrin at physiologic levels of iron saturation may serve as a source of Fe2+ for biological reactions in disease states where activated phagocytes are present and there is a decrease in tissue pH. The unbound iron could participate in biological reactions including promoting propagation of lipid peroxidation reactions or hydroxyl radical formation following reaction with phagocytic cell-derived hydrogen peroxide.
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: J K
authors.initials: JK
authors.lastname: Brieland
authors.forename: J C
authors.initials: JC
authors.lastname: Fantone
mesh_terms: D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*
chemical_list: D014168:Transferrin; D013481:Superoxides; D007501:Iron; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate