1. 59Fe-distribution in conditional ferritin-H–deleted mice
Martin Kistler, Anna Even, Stefan Wagner, Christiane Becker, Depak Darshan, Liviu Vanoaica, Lucas C. Kühn, Klaus Schümann 
Experimental Hematology 
Volume 42, Issue 1, Pages (January 2014)
DOI: /j.exphem
Copyright © 2014 ISEH - Society for Hematology and Stem Cells Terms and Conditions

2. Figure 1
Export of 59Fe from spleen after ferritin-H deletion. 59Fe was injected into mice 28 days before poly-IC injection, and its distribution had reached steady state. Ferritin-H deletion was induced by a single injection of poly-IC on day 1. Splenic 59Fe content was measured in iron-adequate FthΔ/Δ and Fthlox/lox mice before (day 0 = baseline; n = 8) and each day after poly-IC injection (n = 4 for each time point). Data show median and the 25th (box) and 75th (whiskers) percentiles. *Significant differences over time (p < 0.05).
Experimental Hematology  , 59-69DOI: ( /j.exphem )
Copyright © 2014 ISEH - Society for Hematology and Stem Cells Terms and Conditions

3. Figure 2
Changes of plasma 59Fe content in iron-deficient and iron-adequate ferritin-H–deleted (FthΔ/Δ) and control mice (Fthlox/lox). Mice deleted of the ferritin-H gene 7 days before the experiment were compared with nondeleted Fthlox/lox littermates. Mice were injected intravenously with a single dose of 59Fe, and the plasma 59Fe concentration was measured in iron-deficient and iron-adequate FthΔ/Δ and Fthlox/lox mice at different times thereafter (n = 7 for each point in time). Data show median and the 25th (box) and 75th percentile (whiskers). Two-way ANOVA revealed significant interaction between genetic status and iron status regarding 59Fe content in the plasma (12 hours) and liver (24 hours). ° = significant differences between corresponding Fe-status. *Significant differences between corresponding genetic status (p < 0.05). Changes over time: groups of same shade and colour that have no letter in common are significantly different from each other. (A) Plasma 59Fe concentration. (B) Whole-blood 59Fe concentration (= 59Fe in erythrocytes, as 59Fe in plasma was more than an order of magnitude lower at these points in time). (C) Splenic 59Fe concentration. (D) Hepatic 59Fe concentration.
Experimental Hematology  , 59-69DOI: ( /j.exphem )
Copyright © 2014 ISEH - Society for Hematology and Stem Cells Terms and Conditions

4. Figure 3
Comparison of 59Fe-content in heart (A) and kidney (B) of iron-deficient and iron-adequate ferritin-H–deleted and control mice. Mice deleted of the ferritin-H gene 7 days before the experiment were compared with nondeleted Fthlox/lox littermates. Mice were injected with a single dose of 59Fe, and the cardiac (A) and renal (B) 59Fe content was measured in iron-deficient and iron-adequate FthΔ/Δ and Fthlox/lox mice at different times as indicated (n = 7 for each group). Data show median and the 25th and 75th percentiles. Two-way ANOVA revealed significant interaction between genetic status and iron status regarding 59Fe content in the heart (7 days). ° = significant differences between corresponding Fe-status. *Significant differences between corresponding genetic status (p < 0.05). Changes over time: groups of same shade and color that have no letter in common are significantly different from each other.
Experimental Hematology  , 59-69DOI: ( /j.exphem )
Copyright © 2014 ISEH - Society for Hematology and Stem Cells Terms and Conditions

5. Figure 4
Classic scheme of internal iron kinetics [32] and the changes observed in consequence of ferritin-H deletion. Serum iron is distributed preferentially to the erythropoietic bone marrow and, alternatively, directly to iron-dependent enzymes in parenchymal tissues. Erythrocytes reach the circulation after export from the bone marrow. They are preferentially dismantled in the reticuloendothelial system with a minor fraction being channeled via the parenchymal tissues. Released iron quantities are circulated back to the serum iron. In iron deficiency, iron channeling from the serum to the bone marrow and on to circulating erythrocytes is increased (thick, red arrows). Ferritin-H deletion impairs iron storage in parenchymal tissues, as symbolized by two blocking lines between serum iron and parenchymal tissue. Iron reaches the reticuloendothelial system after release from decomposed erythrocytes. 1. Plasma 59Fe content increased in iron-adequate FthΔ/Δ mice after 12 hours (Fig. 2A). There is a transient 59Fe-congestion in the plasma, as the 59Fe-drain into the erythropoietic bone marrow is not increased in the iron-adequate state, and parenchymal 59Fe storage capacity is impaired after ferritin-H deletion in FthΔ/Δ mice; this interaction is significant (two-way ANOVA). 2. Circulating erythrocytes (Fig. 2B). A. 59Fe-content increases in iron-adequate FthΔ/Δ mice after 12 hours, because the alternative shift into ferritin-related iron storage is impaired. B. The 59Fe content is increased in iron-deficient Fthlox/lox mice because of stimulated erythropoiesis in iron deficiency. 3. Splenic 59Fe-content decreased in iron-adequate FthΔ/Δ-mice after 7 days (Fig. 2C). Ferritin-H deletion impairs iron storage in the reticuloendothelial system (RES). The effect is retarded, as 59Fe reaches the RES after the decomposition of erythrocytes, which have a life expectancy of 28 days in mice. 4. Parenchymal organs (Fig. 2D). A. Hepatic 59Fe is lower in iron-deficient FthΔ/Δ as compared to Fthlox/lox mice, because ferritin-H deletion impairs hepatic iron-storage capacity and 59Fe is directed to the erythron. B. Hepatic 59Fe is decreased in iron-deficient compared with iron-adequate FthΔ/Δ mice after 24 hours, as more 59Fe is taken up by the iron-deficient erythron after hepatic ferritin-H deletion. This interaction is significant (two-way ANOVA). C. Cardiac 59Fe is increased in iron-adequate FthΔ/Δ mice, because only half of the ferritin is deleted in this organ and 59Fe drain toward erythropoiesis is not as high as in iron deficiency. This interaction is significant (day 7; two-way ANOVA). (Color version of this figure is available online.)
Experimental Hematology  , 59-69DOI: ( /j.exphem )
Copyright © 2014 ISEH - Society for Hematology and Stem Cells Terms and Conditions