Lipid peroxidation of human granulocytes (PMN) and monocytes by iron complexes.
Because the phagocytic function of non-stimulated human polymorphonuclear granulocytes (PMN) is impaired after incubation with either polynuclear Fe(III) or Fe(II), we decided to study lipid peroxidation of PMN and monocytes by these iron complexes. Lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances and fluorescent compounds. In this study we report that monocytes, isolated in the standard way (EDTA-mediated detachment), release significantly more thiobarbituric acid reactive substances after incubation with iron than PMN. Monocytes, however, isolated without EDTA release the same amount after incubation with iron as PMN. The iron complexes shown to impair phagocyte function also stimulated the peroxidation of membrane lipids. Ascorbic acid in high concentrations enhanced iron-induced lipid peroxidation. Lipid peroxidation induced by ferrous ascorbate (1:20) could be inhibited by catalase, the iron chelators deferoxamine and transferrin, and the hydroxyl radical scavenger thiourea. Mononuclear complexes (ferric citrate 1:20) did not impair granulocyte function and did not induce lipid peroxidation. Our results suggest that impaired phagocyte function in patients with iron overload may be due to non-transferrin bound iron-mediated peroxidation of membrane lipids. However, the lowest amount of ferrous ascorbate (1:20) capable of inducing lipid peroxidation (50 microM) was significantly higher than that which impaired phagocyte function (10 microM).
Hoepelman
I M
IM
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Bezemer
W A
WA
van Doornmalen
E
E
Verhoef
J
J
Marx
J J
JJ
D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D050356:Lipid Metabolism; D008563:Membrane Lipids / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis; D013858:Thiobarbiturates
D005290:Ferric Compounds; D005296:Ferrous Compounds; D008563:Membrane Lipids; D013858:Thiobarbiturates; D007501:Iron; C029684:thiobarbituric acid