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Recombinant human interleukin-3 and granulocyte-macrophage colony-
stimulating factor show common biological effects and binding
characteristics on human monocytes
MJ Elliott, MA Vadas, JM Eglinton, LS Park, LB To, LG Cleland, SC Clark and AF Lopez
Division of Human Immunology, Royal Adelaide Hospital, South Australia.
Two human hemopoietic growth factors involved in monocytopoiesis,
interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor
(GM-CSF) were studied for their ability to stimulate blood monocytes and to
bind to the monocyte membrane. Both cytokines maintained
monocyte/macrophage numbers during long-term culture and increased cell
size as compared with controls. Effects on cell numbers were present at low
cytokine concentrations (6 to 20 pmol/L), whereas enhanced 3H-thymidine
incorporation was observed only at higher concentrations (greater than or
equal to 60 pmol/L). Autoradiographic studies showed only 1% to 3% of
stimulated monocytes with nuclear grains. These results suggest that the
primary mechanism for IL-3 and GM-CSF-induced maintenance of
monocyte/macrophage numbers in humans is through an effect on cell
survival. Surface receptors for both IL-3 and GM-CSF were studied by using
125I-labeled recombinant human (rh) cytokines and performing Scatchard
analyses. Both cytokines showed curvilinear Scatchard plots, and computer
analyses favored a two-site binding model. High-affinity binding data for
125I rhIL-3 (Kd 7.7 to 38.2 pmol/L; receptor number/cell 95 to 580) and for
125I rhGM-CSF (Kd 4.7 to 38.9 pmol/L; receptor number/cell 8 to 67) show
similar binding affinities for the two cytokines but a lower receptor
number/cell for 125I rhGM-CSF. Low-affinity binding characteristics for
125I rhIL-3 (Kd 513 to 939 pmol/L; receptor number/cell 179 to 5,274) and
for 125I rhGM- CSF (Kd 576 to 1,120 pmol/L; receptor number/cell 130 to
657) show a similar pattern for the two cytokines. Specificity of 125I
rhIL-3 and 125I rhGM-CSF binding to monocytes was established by the
ability of the homologous cytokine to inhibit binding and the inability of
a range of other cytokines to compete at 100-fold excess molar
concentration. It is important, however, that binding of 125I rhIL-3 was
partially inhibited by rhGM-CSF and that rhIL-3 partially inhibited binding
of 125I rhGM-CSF to the monocyte membrane under conditions shown to prevent
receptor internalization. The degree of inhibition varied between 25% and
80% in different experiments, and quantitative inhibition experiments
showed that 1,000-fold excess concentrations of competitor failed to
inhibit binding of the heterologous ligand completely. These results
demonstrate that human IL-3 and GM-CSF have similar effects on growth and
survival of human monocytes in vitro and suggest that these and other
common biological effects may be mediated either through a common receptor
or through distinct receptors associated on the monocyte membrane.
Volume 74,
Issue 7,
pp. 2349-2359,
11/15/1989
Copyright © 1989 by The American Society of Hematology
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