The utilization of senescent red cell and hemolysate iron for erythropoiesis.

We report experiments to determine the availability for new hemoglobin production of radioiron from nonviable red cells at various times after deposition in the reticulo-endothelial system and to determine the relative availability of radioiron derived from hemolysates versus that derived from nonviable red cells. When heated nonviable red cells labeled with 59Fe are injected into polycythemic mice the iron is deposited in the reticulo-endothelial system, and less than 1% of it is reutilized for hemoglobin synthesis. If the polycythemic mice are given nonviable red cells 48 hours after exposure to hypoxia, when hemoglobin synthesis is maximal, 25% of the iron is reutilized. When the cells are given 36 hr after exposure to hypoxia, iron reutilization declines to 16%, and when exposure to hypoxia is further delayed, reutilization of the iron falls to a plateau level of 11%. Radioiron from hemolysates, primarily deposited in parenchymal cells of the liver, is less available for new hemoglobin synthesis than is radioiron from nonviable red cells, which is primarily deposited in Kupffer cells of the liver. When transferrin-bound iron is given to polycythemic mice, this iron is also deposited in parenchymal cells of the liver and is also less available for new hemoglobin synthesis. Thus, in relation to an erythropoietic stimulus, the site and time of deposition of iron influence its accessibility for erythropoiesis.