Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels.
OBJECTIVE
Transferrin receptor (TfR) expression in erythroid cells is regulated by a number of factors, including iron status and erythropoietin (Epo) stimulation. However, the impact of these factors on reticulocyte TfR expression in vivo has never been studied. A soluble form of TfR (sTfR) is present in serum in proportion to the mass of cellular TfR. Although sTfR shedding by reticulocytes and erythroblasts has been demonstrated in vitro, the contribution of reticulocyte TfR to serum sTfR has never been evaluated in vivo.


METHODS
We measured directly the total number of reticulocyte TfR in normal rats of different age and iron status, as well as in animals experiencing various conditions and treatments aimed at altering erythropoietic activity and iron status, including rHuEpo therapy, hemolytic anemia, phlebotomies, hypertransfusions, thiamphenicol-induced red cell aplasia or inflammation. In addition, we examined the impact of repeated hypertransfusions with normal, reticulocyte-poor and reticulocyte-rich blood on serum sTfR levels.


RESULTS
The number of TfR molecules per reticulocyte was around 50,000 in young rats but was around 100,000 in older animals. These values remained constant in most conditions and in particular were not influenced by iron supplementation or iron overload. However, functional iron deficiency as well as rHuEpo therapy resulted in increased reticulocyte TfR expression. In addition, TfR numbers in reticulocytes were elevated in the early phase of recovery after acute hemolysis or red cell aplasia but normalized soon after. Hypertransfusion experiments clearly demonstrated that reticulocytes can contribute substantially to sTfR levels in vivo.


CONCLUSIONS
TfR numbers are regulated in vivo by the same factors as in vitro, in particular iron deficiency and erythropoietin stimulation. Circulating reticulocytes contribute significantly to serum sTfR levels.
Department of Medicine, Division of Hematology, University of Liège, Belgium.
S
S
R'zik
M
M
Loo
Y
Y
Beguin
D000818:Animals; D019190:Iron Overload / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin / Q000097:blood*; D012156:Reticulocytes / Q000378:metabolism*; D012995:Solubility
D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin