Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels

Background and Objectives. Transferrin receptor (TfR) expression in erythro id cells is regulated by a number of factors, including iron status and ery thropoietin (Epo) stimulation. However, the impact of these factors on reti culocyte TfR expression in vivo has never been studied. A soluble form of T fR (sTfR) is present in serum in proportion to the mass of cellular TfR. Al though sTfR shedding by reticulocytes and erythroblasts has been demonstrat ed in vitro, the contribution of reticulocyte TfR to serum sTfR has never b een evaluated in vivo. Design and methods. We measured directly the total number of reticulocyte T fR in normal rats of different age and iron status, as well as in animals e xperiencing various conditions and treatments aimed at altering erythropoie tic activity and iron status, including rHuEpo therapy, hemolytic anemia, p hlebotomies, hypertransfusions, thiamphenicol-induced red cell aplasia or i nflammation. In addition, we examined the impact of repeated hypertransfusi ons with normal, reticulocyte-poor and reticulocyte-rich broad on serum sTf R levers. Results. The number of TfR molecules per reticulocyte was around 50,000 in young rats but was around 100,000 in order animals. These values remained c onstant in most conditions and in particular were not influenced by iron su pplementation or iron overload, However, functional iron deficiency as well as rHuEpo therapy resulted in increased reticulocyte TfR expression. In ad dition, TfR numbers in reticulocytes were elevated in the early phase of re covery after acute hemolysis or red cell aplasia but normalized soon after. Hypertransfusion experiments clearly demonstrated that reticulocytes can c ontribute substantially to sTfR levers in vivo. Interpretation and conclusions. TfR numbers are regulated in vivo by the sa me factors as in vitro, in particular iran deficiency and erythropoietin st imulation. Circulating reticulocytes contribute significantly to serum sTfR levels. (C) 2001, Ferrata Storti Foundation.