Iron absorption and distribution in TNF(DeltaARE/+) mice, a model of chronic inflammation.
Hemizygous TNF(DeltaARE/+) mice are a murine model for chronic inflammation. We utilized these animals to study iron-kinetics and corresponding protein expression in an iron-deficient and iron-adequate setting. (59)Fe-absorption was determined in ligated duodenal loops in vivo. Whole body distribution of i.v. injected (59)Fe was analysed, and the organ specific expression of ferroportin, transferrin receptor-1, hepcidin and duodenal DMT-1 was quantified by real-time PCR and Western blotting. Duodenal (59)Fe-lumen-to-body transport was not affected by the genotype. Duodenal (59)Fe-retention was increased in TNF(DeltaARE/+) mice, suggesting higher (59)Fe-losses with defoliated enterocytes. Iron-deficiency increased duodenal (59)Fe-lumen-to-body transport, and higher duodenal (59)Fe-tissue retention went along with higher duodenal DMT-1, ferroportin, and liver hepcidin expression. TNF(DeltaARE/+) mice significantly increase their (59)Fe-content in inflamed joints and ilea, and correspondingly reduce splenic (59)Fe-content. Leukocyte infiltrations in the joints suggest a substantial shift of iron-loaded RES cells to inflamed tissues as the underlying mechanism. This finding was paralleled by increased non-haem iron content in joints and reduced haemoglobin and haematocrit concentrations in TNF(DeltaARE/+) mice. In conclusion, erythropoiesis in inflamed TNF(DeltaARE/+) mice could be iron-limited due to losses with exfoliated iron-loaded enterocytes and/or to increased iron-retention in RES cells that shift from the spleen to inflamed tissues.
Schümann
Klaus
K
Science Centre Weihenstephan, Technical University Munich, 85350 Freising, Germany. kschuemann@schuemann-muc.de
Herbach
Nadia
N
Kerling
Christina
C
Seifert
Markus
M
Fillebeen
Carine
C
Prysch
Isabella
I
Reich
Jens
J
Weiss
Günter
G
Pantopoulos
Kostas
K
D000042:Absorption; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism; D064451:Hepcidins; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D007501:Iron / Q000493:pharmacokinetics*; D051379:Mice; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D014409:Tumor Necrosis Factor-alpha; D007501:Iron