Iron loading of alveolar macrophages in vivo significantly altered their ability to respond to various inflammatory stimuli. This was exemplified by reduced synthesis of inducible nitric oxide synthase after stimulus with lipopolysaccharide and interferon gamma, and an enhanced activation of nuclear factor kappa B in the absence of tumour necrosis factor alpha stimulation, and enhanced production of reactive oxygen species after activation with activated zymosan and PMA. Such results may indicate an imbalance in the production of reactive oxygen and reactive nitrogen species generated by the iron-loaded macrophages after an appropriate stimulus.
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 (NFkappaB). 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.
The effects of a single intramuscular iron dose, 10mg, to pregnant rats on Day of pregnancy, on the
outcome of pregnancy, with respect to foetal weight and mother’s immune function has been investigated.
Despite significantly elevated hepatic iron stores after iron supplementation in pregnant rats this had no
significant effect upon blood haemoglobin or transferrin saturation levels. However the mean weight of the
foetuses at Day 20-21 was significantly lower than that of the non-supplemented pregnant rats. Iron
supplements significantly increased the activity of NADPH oxidase in the maternal alveolar macrophages,
the primary event in the formation of the phagolysosome to combat invading organisms. However inducible
nitric oxide synthase activity was significantly reduced in these macrophages as shown by decreases in LPSinduced
and LPS+IFNγ-induced NOS activation. Iron supplementation to rats of normal iron status at the
commencement of pregnancy did not show any beneficial effects to either the foetus or the mother.
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