EXPRESSION AND MODULATION OF IL-3 AND GM-CSF RECEPTORS IN HUMAN GROWTH-FACTOR DEPENDENT LEUKEMIC-CELLS

Summary From the interleukin‐3 (IL‐3) responsive human myeloid cell line M‐07 we derived a subclone, named M‐07e. which is fully dependent for growth and survival on either granulocyte‐macrophage colony stimulating factor (GM‐CSF) or IL‐3. In this paper the expression, specificity and modulation of GM‐CSF and IL‐3 receptors on M‐07e cells are described. The specificity of the binding was demonstrated by the failure of other cytokines to compete, at 4°C. with GM‐CSF or IL‐3 receptors. In addition, IL‐3 was found to compete as well as GM‐CSF for GM‐CSF receptors while GM‐CSF was a weak competitor for IL‐3 receptors. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high‐affinity GM‐CSF binding sites (405 ± 2 74 sites per cell, dissociation constant at the equilibrium 52 ± 20 PM) and the presence of high and low‐affinity regions for IL‐3 binding sites (2 7 ± 12 and 416 ± 92 sites per cell for the high and low affinity regions respectively, dissociation constant at the equilibrium, 58 ± 22 PM and 5.7 ± 2.0 nM respectively). Finally, in agreement with the hierarchical down‐modulation model, we found that IL‐3 can down‐modulate both IL‐3 and GM‐CSF receptors while GM‐CSF can down‐modulate only its own receptors. The present results suggest that M‐07e cells, in spite of their neoplastic nature, share, with murine bone marrow cells, similar growth factor receptor regulatory mechanisms. This cell line may be regarded as a candidate model to investigate the physiological events triggered by growth factors binding to human haemopoietic cells. Copyright © 1990, Wiley Blackwell. All rights reserved