02677nas a2200421   4500008004100000022001400041245009700055210006900152260001200221300001200233490000700245520147600252653002501728653001201753653003601765653003001801653001401831653001401845653003301859653001401892653002101906653000901927653001501936653001601951653000901967653001701976653002201993653002702015653001602042653003202058100001902090700002102109700001902130700002102149700001802170700001902188856004802207       2008                        eng d  a0014-298000aInterferon-gamma limits the availability of iron for intramacrophage Salmonella typhimurium.0 aInterferongamma limits the availability of iron for intramacroph  c07/2008  a1923-360 v383 a<p>In stimulating effector functions of mononuclear phagocytes, IFN-gamma is of pivotal importance in host defense against intramacrophage pathogens including salmonellae. As the activity of IFN-gamma is modulated by iron and since a sufficient availability of iron is essential for the growth of pathogens, we investigated the regulatory effects of IFN-gamma on iron homeostasis and immune function in murine macrophages infected with Salmonella typhimurium. In Salmonella-infected phagocytes, IFN-gamma caused a significant reduction of iron uptake via transferrin receptor 1 and resulted in an increased iron efflux caused by an enhanced expression of the iron exporter ferroportin 1. Moreover, the expression of haem oxygenase 1 and of the siderophore-capturing antimicrobial peptide lipocalin 2 was markedly elevated following bacterial invasion, with IFN-gamma exerting a super-inducing effect. This observed regulatory impact of IFN-gamma reduced the intracellular iron pools within infected phagocytes, thus restricting the acquisition of iron by engulfed Salmonella typhimurium while concomitantly promoting NO and TNF-alpha production. Our data suggest that the modulation of crucial pathways of macrophage iron metabolism in response to IFN-gamma concordantly aims at withdrawing iron from intracellular Salmonella and at strengthening macrophage immune response functions. These regulations are thus consistent with the principles of nutritional immunity.</p>10aAcute-Phase Proteins10aAnimals10aAntimicrobial Cationic Peptides10aCation Transport Proteins10aCell Line10aFerritins10aHeme Oxygenase (Decyclizing)10aHepcidins10aInterferon-gamma10aIron10aLipocalins10aMacrophages10aMice10aNitric Oxide10aOncogene Proteins10aSalmonella typhimurium10aTransferrin10aTumor Necrosis Factor-alpha1 aNairz, Manfred1 aFritsche, Gernot1 aBrunner, Peter1 aTalasz, Heribert1 aHantke, Klaus1 aWeiss, Günter  uhttp://www.ncbi.nlm.nih.gov/pubmed/1858132302450nas a2200397   4500008004100000022001400041245010000055210006900155260001200224300001000236490000700246520132400253653001201577653002701589653002401616653001601640653001301656653003101669653001601700653001601716653000901732653001801741653001601759653000901775653002301784653003001807653000801837100001701845700002301862700001901885700002001904700001801924700001901942700001901961856007201980       2005                        eng d  a0168-827800aPathways for the regulation of body iron homeostasis in response to experimental iron overload.0 aPathways for the regulation of body iron homeostasis in response  c10/2005  a711-90 v433 aBACKGROUND/AIMS:
Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions.
METHODS:
To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days.
RESULTS:
Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced.
CONCLUSIONS:
Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.10aAnimals10aDisease Models, Animal10aDisease Progression10aDNA Primers10aDuodenum10aGene Expression Regulation10aHepatocytes10aHomeostasis10aIron10aIron Overload10aMacrophages10aMice10aMice, Inbred C57BL10aPolymerase Chain Reaction10aRNA1 aTheurl, Igor1 aLudwiczek, Susanne1 aEller, Philipp1 aSeifert, Markus1 aArtner, Erika1 aBrunner, Peter1 aWeiss, Günter  uhttp://www.sciencedirect.com/science/article/pii/S0168827805003168#