Related Experiment Videos
Polynuclear iron complexes impair the function of polymorphonuclear granulocytes
I M Hoepelman1, E Y Jaarsma, J Verhoef
1Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Abstract:
In a previous study we showed that the phagocytic function of non-stimulated PMN was impaired after incubation with high concentrations (200 microM) of polynuclear Fe(III), probably as a result of continuous generation of small amounts of superoxide and subsequent formation of hydroxyl radicals (Van Asbeck et al, 1984b). Because polynuclear Fe(III) complexes may not be available for biological reactions we have studied the effects of polynuclear and mononuclear iron(III) on the PMN. Fe(III) in its polynuclear form (Fe:citrate 1:1) was deleterious for the phagocytic function of PMN, while the mononuclear form (Fe:citrate 1:20) was not toxic. Binding affinity of polynuclear Fe(III) for PMN was higher than of mononuclear Fe(III), and a considerable amount of bound Fe(III) was found in the cytosolic fraction of non-stimulated PMN. Limit dilution analysis of polynuclear complexes revealed that concentrations as low as 25 microM Fe(III) significantly impaired phagocytic function. The molecular weight of these complexes is similar to that of the non-transferrin plasma iron found in the serum of patients with iron overload. The toxic effects of small polynuclear non-transferrin plasma Fe(III) complexes on PMN function may contribute to the development of infections in patients with iron overload.
Insights
Polynuclear iron(III) complexes impair polymorphonuclear (PMN) cell function at low concentrations, unlike mononuclear forms. This impaired PMN function may increase infection risk in iron overload patients.
Area of Science:
- Immunology
- Biochemistry
- Hematology
Background:
- Previous studies indicated high polynuclear iron(III) concentrations impair polymorphonuclear (PMN) phagocytic function.
- The biological availability of polynuclear iron(III) complexes was questioned.
Purpose of the Study:
- To investigate the distinct effects of polynuclear and mononuclear iron(III) on PMN function.
- To determine the binding affinity and cellular localization of different iron(III) forms.
- To assess the impact of low polynuclear iron(III) concentrations on PMN phagocytosis.
Main Methods:
- Incubation of non-stimulated PMN with varying concentrations and forms of iron(III) (polynuclear and mononuclear citrate complexes).
- Assessment of PMN phagocytic function.
- Measurement of iron(III) binding affinity to PMN and its cellular distribution.
- Limit dilution analysis of polynuclear iron(III) complexes.
Main Results:
- Polynuclear iron(III) (Fe:citrate 1:1) significantly impaired PMN phagocytic function, while mononuclear iron(III) (Fe:citrate 1:20) did not.
- Polynuclear iron(III) exhibited higher binding affinity for PMN and was found in the cytosolic fraction.
- Concentrations as low as 25 microM Fe(III) in polynuclear form impaired phagocytic function.
- The molecular weight of toxic polynuclear complexes resembles non-transferrin plasma iron in iron overload.
Conclusions:
- Polynuclear iron(III) complexes are toxic to PMN function at lower concentrations than previously thought.
- The impaired PMN function due to polynuclear iron(III) may contribute to increased infection susceptibility in iron overload conditions.