Dynamics of erythropoietin receptor expression on erythropoietin-
responsive murine cell lines
VC Broudy, B Nakamoto, N Lin and T Papayannopoulou
Division of Hematology, University of Washington School of Medicine,
Seattle 98195.
We examined erythropoietin receptor expression in two murine cell lines,
B6SUtA and DA-1, that respond to erythropoietin in different ways. While
B6SUtA cells undergo erythroid differentiation with limited proliferation
after addition of erythropoietin, DA-1 cells show only a proliferative
response. Equilibrium binding experiments with 125I- erythropoietin
revealed that both B6SUtA and DA-1 cells express a single class of
erythropoietin receptors. In the absence of erythropoietin, B6SUtA cells
exhibited 145 receptors per cell with a dissociation constant (kd) of 380
pmol/L. Six days after induction with erythropoietin, the B6SUtA cells
displayed 310 receptors per cell without a change in binding affinity;
exposure to erythropoietin also increased cellular hemoglobin content. DA-1
cells adapted to erythropoietin-dependent growth over a period of months
and exhibited a progressive increase in erythropoietin receptor expression,
from 85 per cell (kd = 540) to 550 per cell (kd = 530), although the cells
remained uniformly benzidine-negative. We interpret the data with B6SUtA
cells to indicate that early erythroid differentiation stages are attended
by an increase in erythropoietin receptor display, coordinate with the
initiation of expression of erythroid-specific genes. In contrast, the
results with DA-1 cells are most compatible with clonal selection as the
mechanism underlying enhanced receptor expression. Thus, display of the
erythropoietin receptor is dynamic and can be modulated during the course
of erythropoietin-induced differentiation.
Volume 75,
Issue 8,
pp. 1622-1626,
04/15/1990
Copyright © 1990 by The American Society of Hematology
