Abstract
The effects of changes in macrophage iron status, induced by single or multiple iron injections, iron depletion or pregnancy, on both immune function and mRNA expression of genes involved in iron influx and egress have been evaluated. Macrophages isolated from iron deficient rats, or pregnant rats at day 21 of gestation, either supplemented with a single dose of iron dextran, 10 mg, at the commencement of pregnancy, or not, showed significant increases of macrophage ferroportin mRNA expression, which was paralleled by significant decreases in hepatic Hamp mRNA expression. IRP activity in macrophages was not significantly altered by iron status or the inducement of pregnancy ± a single iron supplement. Macrophage immune function was significantly altered by iron supplementation and pregnancy. Iron supplementation, alone or combined with pregnancy, increased the activities of both NADPH oxidase and nuclear factor kappa B (NFκB). In contrast, the imposition of pregnancy reduced the ability of these parameters to respond to an inflammatory stimuli. Increasing iron status, if only marginally, will reduce the ability of macrophages to mount a sustained response to inflammation as well as altering iron homeostatic mechanisms.
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Abbreviations
- NO:
-
Nitric oxide
- DcytB:
-
Duodenal cytochrome B
- DMEM:
-
Dubecco’s modified eagle medium
- DMT1:
-
Divalent metal-ion transporter 1
- EDTA:
-
Ethylenediamine tetra acetate
- fmlp:
-
N formyl methionyl leucyl phenylalanine
- HEPES:
-
N-2-hydroxylethylpiperazine
- ICP-AES:
-
Inductively coupled plasma-atomic emission spectroscopy
- IRP:
-
Iron regulatory protein
- IRE:
-
Iron regulatory element
- IFNγ:
-
Interferon gamma
- LNMA:
-
NG-methyl-l-arginine
- LPS:
-
Lipopolysaccharide
- NFκB:
-
Nuclear factor kappa B
- NOS:
-
Nitric oxide synthase
- PMA:
-
Phorbol-12 myristate-13 acetate
- RT-PCR:
-
Reverse transcriptase polymerase chain reaction
- TIBC:
-
Total iron binding capacity
- TfR1:
-
Transferrin receptor 1
- TNFα:
-
Tumor necrosis factor alpha
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Acknowledgements
This work was supported by EC grant QLK1-CT-1999-00337. We are grateful to Vifor Pharmaceuticals for the supply of iron dextran and to Dr. N. Beaumont for advice with the RT-PCR assays.
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Ward, R.J., Wilmet, S., Legssyer, R. et al. Effects of marginal iron overload on iron homeostasis and immune function in alveolar macrophages isolated from pregnant and normal rats. Biometals 22, 211–223 (2009). https://doi.org/10.1007/s10534-008-9155-6
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DOI: https://doi.org/10.1007/s10534-008-9155-6