Surface Remodeling vs. Whole-Cell Hemolysis of Reticulocytes Produced With Erythroid Stimulation or Iron Deficiency Anemia

³²P in membrane phosphatidylethanolamine (PE) and red cell ¹⁴C, reflecting cytoplasmic hemoglobin, were measured sequentially in rats given transfusions of doubly-labeled reticulocytes. With reticulocytes from normal rats there was a small decline in the levels of both the membrane and the cytoplasmic labels; the changes were almost parellel, although loss of membrane PE-³²P exceeded that of ¹⁴C to a small extent. By contrast, with "stress reticulocytes" from bled donors, there was a markedly disproportionate loss of the membrane label; this asymmetrical loss of membrane material was diminished when recipients had been splenectomized. With transfusions of doubly-labeled reticulocytes from rats with severe iron deficiency anemia, there was a marked loss of both membrane PE-³²P and red cell ¹⁴C which was only moderately asymmetrical. The asymmetrical loss of the membrane label found with stress reticulocytes supports the conclusion that these cells undergo a process of surface remodeling during their maturation in the peripheral blood. The spleen is partly responsible for this process. Normal reticulocytes also appear to undergo a minor degree of remodeling. On the other hand, the almost symmetrical loss of membrane and cytoplasmic label observed with reticulocytes from iron deficient rats indicates that many of the cells in this model of ineffective erythropoiesis are hemolyzed in their entirety. These experiments demonstrate that stress reticulocytes differ under different conditions and may lose cellular material by two, possibly interrelated, mechanisms: surface remodeling or whole-cell hemolysis.