Polynuclear iron complexes impair the function of polymorphonuclear granulocytes

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.