Clin Exp Immunol. 2004 Jul;137(1):109-16. Related Articles, Links
Iron down-regulates macrophage anti-tumour activity by
blocking nitric oxide production.
Harhaji L, Vuckovic O, Miljkovic D, Stosic-Grujicic S,
Trajkovic V.
Department of Neurobiology and Immunology, Institute for
Biological Research, University of Belgrade, Belgrade,
Serbia and Montenegro.
SUMMARY Although the inhibitory effect of iron on macrophage
production of tumoricidal free radical nitric oxide (NO) has
been reported, its possible influence on macrophage anti-
tumour activity has not been established. In the present
study, FeSO(4) markedly reduced IFN-gamma + LPS-induced NO
synthesis in mouse and rat macrophages. The effect of iron
coincided with the loss of macrophage cytotoxic activity
against NO-sensitive C6 rat astrocytoma and L929 mouse
fibrosarcoma cell lines, as measured by MTT assay for
cellular respiration and the crystal violet test for cell
viability. Tumour cell survival did not improve further in
the presence of FeSO(4) if macrophage NO release and
cytotoxicity were already blocked by aminoguanidine. In
accordance with the results obtained with exogenous iron,
cell membrane permeable iron chelator o-phenanthroline
enhanced both macrophage NO release and anti-tumour
activity. Iron also down-regulated NO production and
increased the viability of L929 fibrosarcoma cells
stimulated with IFN-gamma + LPS in the absence of
macrophages. However, neither NO release nor cell viability
was affected by iron addition to cultures of the C6
astrocytoma cell line. Iron was unable to prevent L929 and
C6 cell death induced by the NO releasing chemicals SNP and
SIN-1, indicating that iron-mediated inhibition of NO
synthesis, rather than interference with its cytotoxic
action, was responsible for the protection of tumour cells.
Collectively, these results indicate that iron might protect
tumour cells by reducing both macrophage and tumour cell-
derived NO release.
PMID: 15196250 [PubMed - in process]
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