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Common binding structure for granulocyte macrophage colony-stimulating
factor and interleukin-3 on human acute myeloid leukemia cells and
monocytes
LM Budel, O Elbaz, H Hoogerbrugge, R Delwel, LA Mahmoud, B Lowenberg and IP Touw
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3
(IL-3) control the proliferation of human acute myeloid leukemia (AML)
cells in vitro. Previously, we have shown that receptors for GM-CSF and
IL-3 are often coexpressed on AML cells. Here we present experiments with
purified AML blasts, normal monocytes, and granulocytes that were conducted
to analyze the properties of GM-CSF and IL-3 binding proteins in more
detail. On AML cells from eight cases we demonstrate two types of GM-CSF
receptors: one with low affinity (dissociation constant [kd] 5.1 to 24.8
nmol/L) and one with a high affinity (kd 31 to 104 pmol/L). These AML cells
also expressed high affinity receptors for IL-3 (kd 24 to 104 pmol/L).
Cross-competition experiments showed that an excess concentration of
nonlabeled IL-3 completely prevented the high affinity binding of
radiolabled GM-CSF. This competition occurred at 37 degrees C as well as 4
degrees C. Low affinity GM-CSF binding was not affected by IL-3. Binding of
radiolabeled IL-3 could be prevented by nonlabeled GM-CSF. In certain
cases, this competition was complete, whereas in others only partial (49%
to 77%) reduction of the radiolabeled IL-3 binding was seen. On the basis
of these ligand binding features, we propose the existence of three
receptor types on AML cells: (1) low affinity GM-CSF receptors that do not
bind IL-3, (2) dual high affinity GM-CSF/IL-3 receptors, and (3) high
affinity IL-3 receptors that do not bind GM-CSF. We could also demonstrate
these receptor types on normal monocytes. In addition, a fourth type of
receptor was apparent on normal granulocytes (4), incapable of binding IL-3
and with an intermediate affinity for GM-CSF (approximately 400 pmol/L).
Chemical crosslinking showed that GM-CSF and IL-3 both bind to proteins
with molecular weight values of 130, 105, and 75, which provides additional
evidence for the existence of a common GM-CSF/IL-3 receptor complex.
Volume 75,
Issue 7,
pp. 1439-1445,
04/01/1990
Copyright © 1990 by The American Society of Hematology
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