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Effect of iron on polymorphonuclear granulocyte phagocytic capacity: role of oxidation state and effect of ascorbic
I M Hoepelman1, E Y Jaarsma, J Verhoef
1Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Abstract:
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 concentrations as low as 1-10 microM. 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 mediated 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.
Insights
Iron (II) significantly impairs polymorphonuclear granulocyte (PMN) function and bacterial uptake. Ascorbic acid exacerbates this iron toxicity, suggesting direct membrane interaction rather than solely oxygen radical involvement.
Area of Science:
- Immunology
- Biochemistry
Background:
- Iron (III) is known to impair polymorphonuclear granulocyte (PMN) function.
- The specific effects of iron (II) on PMN membrane function and phagocytosis require further elucidation.
Purpose of the Study:
- To investigate the impact of iron (II) on the phagocytic capacity of PMN.
- To explore the role of ascorbic acid and iron-oxygen intermediates in iron-mediated PMN dysfunction.
Main Methods:
- Assessing the uptake of radiolabelled Staphylococcus aureus by PMN.
- Evaluating the effects of iron (II), ferrous ascorbate, and oxygen-free radical scavengers on PMN function.
- Comparing iron's effect on PMN from healthy individuals versus a patient with chronic granulomatous disease.
Main Results:
- Iron (II) significantly impaired PMN phagocytic function and bacterial uptake.
- Ferrous ascorbate (1:20 molar ratio) demonstrated toxicity at low iron concentrations (1-10 microM).
- Toxicity was mitigated by desferrioxamine or transferrin, but not entirely prevented by radical scavengers for ferrous ascorbate.
Conclusions:
- Iron (II) directly impairs PMN membrane function, independent of oxygen radical generation.
- Ascorbic acid can potentiate iron (II) toxicity, indicating complex interactions.
- Iron-mediated PMN impairment involves direct membrane interaction beyond reactive oxygen species.