Effect of iron on polymorphonuclear granulocyte phagocytic capacity: Role of oxidation state and effect of ascorbic acid

It has been shown that iron (III) impairs the function of polymorphonuclear granulocytes (PMN). We have studied the effect of iron (II), on the membrane function of PMN, by assessing the uptake of radiolabelled Staphylococcus aureus by these cells. Iron (II), significantly impaired PMN phagocytic function. Addition of ascorbic acid reduced uptake further. Ferrous ascorbate, molar ratio 1:20, impaired phagocytic capacity of PMN significantly at iron concentration as low as 1-10 μM. The toxic effect of iron (II) was not observed when desferrioxamine or transferrin was present in the incubation medium. The oxygen-free radical scavengers thiourea, mannitol and catalase prevented toxicity medited by ferrous ammoniumsulphate but not by ferrous ascorbate (molar ratio of 1:20). Although high concentrations of ascorbic acid inhibited the generation of ·OH and also the formation of the DMPO-·OH adduct by zymosan stimulated PMN, toxicity of iron increased. Iron (II) impaired the uptake of S. aureus by PMN of a patient with chronic granulomatous disease while iron (III) did not. Iron mediated impairment of PMN function is not only a result of the generation of toxic oxygen metabolites but also of direct interaction of iron (II) or an iron (II)-oxygen intermediate with molecules of the cell membrane.