Factors Involved in the Regulation of Iron Transport through Reticuloendothelial Cells

Abstract

The effects of various maneuvers on the handling of ⁵⁹Fe-labeled heat-damaged red cells (⁵⁹Fe HDRC) by the reticuloendothelial system were studied in rats. Raising the saturation of transferrin with oral carbonyl iron had little effect on splenic release of ⁵⁹Fe but markedly inhibited hepatic release. Splenic ⁵⁹Fe release was, however, inhibited by the prior administration of unlabeled HDRC or by the combination of carbonyl iron and unlabeled HDRC. When carbonyl iron was administered with unlabeled free hemoglobin, the pattern of ⁵⁹Fe distribution was the same as that observed when carbonyl iron was given alone. ⁵⁹Fe ferritin was identified in the serum after the administration of ⁵⁹Fe HDRC but the size of the fraction was not affected by raising the saturation of transferrin. Sizing column analyses of tissue extracts from the spleen at various times after the administration of ⁵⁹Fe HDRC revealed a progressive shift from hemoglobin to ferritin, with only small amounts present in a small molecular weight fraction. The small molecular weight fraction was greater in hepatic extracts, with the difference being marked in animals that had received prior carbonyl iron. The increased hepatic retention of ⁵⁹Fe associated with a raised saturation of transferrin was reduced by a hydrophobic ferrous chelator (2,2′-bipyridine), a hydrophilic ferric chelator (desferrioxamine), and an extracellular hydrophilic ferric chelator (diethylene-triaminepentacetic acid). Transmembrane iron transport did not seem to be a rate-limiting factor in iron release, since no differences in ⁵⁹Fe membrane fractions were noted in the different experimental settings. These findings are consistent with a model in which RE cells release iron from catabolized red cells at a relatively constant rate. When the saturation of transferrin is raised, a significant proportion of the iron is transported from the spleen to the liver either in small molecular weight complexes or in ferritin. Although a saturated transferrin has no effect on the release of iron from reticuloendothelial cells, prior loading with HDRC conditions them to release less iron.