Fe-59-distribution in conditional ferritin-H-deleted mice

The objective was to explore how ferritin-H deletion influences Fe-59-distribution and excretion-kinetics in mice. Kinetics of Fe-59-release from organs, whole-body excretion, and distribution-kinetics of intravenously injected Fe-59 trace amounts were compared in iron-deficient and iron-replete mice with (Fth(Delta/Delta)) and without (Fth(lox/lox)) conditional Mx-Cre-induced ferritin-H deletion. Fe-59 was released from spleen and liver beginning on day 2 and day 5 after ferritin-H deletion, respectively, but was not excreted from the body. Plasma-Fe-59 was cleared significantly faster in iron-deficient Fth(Delta/Delta)-mice than in iron-adequate Fth(lox/lox)-controls. Fe-59-distribution showed a transient peak (e.g., in heart, kidney, muscle) in Fth(lox/lox) control mice, but not in ferritin-H deleted Fth(Delta/Delta) mice 24 hours after Fe-59 injection. Fe-59 uptake into the liver and spleen was significantly lower in iron-deficient Fth(Delta/Delta) than in Fth(lox/lox) mice 24 hours and 7 days after injection, respectively, and rapidly appeared in circulating erythrocytes instead. The rate of Fe-59 release after ferritin-H deletion supports earlier data on ferritin turnover in mammals; released Fe-59 is not excreted from the body. Instead, Fe-59 is channeled into erythropoiesis and circulating erythrocytes significantly more extensively and faster. Along with a lack of transient interim Fe-59 storage (e.g., in the heart and kidney), this finding is evidence for ferritin-related iron storage-capacity affecting rate and extent of iron utilization. (C) 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.