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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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Who loves ya.
Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking
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]
--------------------------------------------------------------------------
------
Who loves ya.
Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking
