IL-3 inhibits the binding of GM-CSF to AML blasts, but the two cytokines act synergistically in supporting blast proliferation

• Published in: Leukemia Vol. 4; no. 5; p. 329
• Main Authors: Onetto-Pothier, N, Aumont, N, Haman, A, Park, L, Clark, S C, De Léan, A, Hoang, T
• Format: Journal Article
• Language: English
• Published: England 01.05.1990
• Subjects: Binding Sites; Binding, Competitive; Cell Division; Colony-Stimulating Factors - metabolism; Colony-Stimulating Factors - pharmacology; Drug Synergism; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances - metabolism; Growth Substances - pharmacology; Humans; Interleukin-3 - metabolism; Interleukin-3 - pharmacology; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Neutrophils - metabolism; Receptors, Immunologic - metabolism; Receptors, Interleukin-3; Tumor Cells, Cultured - metabolism; Tumor Cells, Cultured - pathology
• ISSN: 0887-6924; 1476-5551

Equilibrium binding of 125I-labeled recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) to the blast cells of acute myeloblastic leukemia (AML) revealed the presence of two classes of binding components of high and low affinity, with dissociation constants (Kd) in the range of 5-10 pM and 1-10 nM, respectively. Specificity studies revealed that interleukin-3 (IL-3) could partially inhibit the binding of GM-CSF to AML blasts and to the cells of the leukemic lines M07-E, KG-1, and HL-60. The inhibition of GM-CSF binding by IL-3 was directly dependent on the presence of IL-3 receptors. Analysis of competition curves indicated that the Kd and the number of binding sites per cell of unlabeled and iodinated GM-CSF were identical. In contrast, the inhibition of GM-CSF binding by IL-3 was mediated by IL-3 occupancy of a high affinity receptor only, with the same number of sites as the high affinity GM-CSF receptor but a slightly higher Kd. Despite this competitive binding, IL-3 augmented AML blast proliferation in the presence of GM-CSF, indicating that the two growth factors have converging pathways in supporting blast proliferation. In striking contrast to AML blasts, GM-CSF binding to neutrophils was compatible with the presence of only one class of binding site of intermediate affinity (Kd approximately 100-160 pM). Furthermore, IL-3 does not compete for the binding of GM-CSF to neutrophils.