RECYCLING OF RETICULOENDOTHELIAL IRON IN VIVO IN THE ABSENCE OF APOTRANSFERRIN

Abstract

Plasma iron is largely derived from macrophage recycling of iron from red blood cells (RBC). We hypothesize that iron-free transferrin (apoTf) is required for iron distribution to the erythron but is not obligatory for release of macrophage iron. We tested this hypothesis using a strain of mutant mice with atransferrinemia. These mice have serum Tf concentrations of 1% or less, suffer from iron-limited erythropolesis but exhibit parenchymal organ iron-overload. We synthesized ⁵⁹Fe-methemalbumin, incorporated it in vitro into sheep RBC and coated the sheep RBC with IgG. Coated and uncoated sheep RBC were injected IV and IP respectively into both normal and atransferrinemic (Hpx) mice. At intervals the quantity of ⁵⁹Fe in the blood and selected tissues was determined. In normal mice the ⁵⁹Fe disappeared from blood with a t1/2 of 3.1 min. By 30 min. 20-30% of the injected counts were found in liver and spleen. By 72h, hepatic and splenic iron fell and 15% of the injected counts were detected in RBC. Hpx animals cleared injected sheep RBC and deposited ⁵⁹Fe in the liver and spleen in a similar way. By contrast, Hpx mice were unable to recycle iron to the erythron (<1%) but did recycle iron to other organs. By 1 wk, 6% of the injected counts were found in the acinar cells of the pancreas. These data indicate that apoTf is not required for recycling of RES iron to the parenchymal organs but is required for recycling to the erythron. Iron distribution in the Hpx mouse closely resembles that in children with congenital atransferrinemia.

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