Expression and modulation of IL‐3 and GM‐CSF receptors in human growth factor dependent leukaemic cells

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Abstract
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.

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