Polynuclear iron complexes impair the function of polymorphonuclear granulocytes.
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.
Hoepelman
I M
IM
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Jaarsma
E Y
EY
Verhoef
J
J
Marx
J J
JJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008970:Molecular Weight; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*
D005290:Ferric Compounds; C025314:ferric citrate; D007501:Iron