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Interleukin-1 (IL-1) directly and indirectly promotes hematopoietic cell
growth through type I IL-1 receptor
K Hestdal, FW Ruscetti, R Chizzonite, M Ortiz, JM Gooya, DL Longo and JR Keller
Laboratory of Molecular Immunoregulation, Biological Response Modifiers
Program, Frederick, MD.
Interleukin-1 (IL-1) has been shown to stimulate hematopoietic progenitor
cell growth both in vitro and in vivo. Although IL-1 alone lacks the
ability to promote hematopoietic progenitor growth in vitro, it is a potent
synergistic factor in combination with other colony- stimulating factors
(CSFs). Because it was unknown whether type I (p80), type II (p68), or
other IL-1-binding proteins mediated the synergistic effects of IL-1 on
purified progenitor cells, we used the difference in immunoreactivity
between type I and type II IL-1 receptor (IL-1R) to better assess the role
of these receptors in hematopoietic progenitor growth. Therefore, the
synergistic effects of IL-1 alpha on IL-3-, CSF-1-, and granulocyte
macrophage (GM)-CSF-induced progenitor growth, both in CFU-c and
single-cell assays, were determined in the presence of monoclonal
antibodies (MoAbs) 35F5 and 4E2 that block the binding of IL-1 alpha to
type I and type II IL-1R, respectively. The synergistic effect of IL-1
alpha on IL-3 responsive Lin- and Lin(-)-Thy- 1+ progenitors was indirectly
mediated and could be inhibited by MoAb 35F5. In contrast, IL-1 alpha
directly synergized with CSF-1 and GM-CSF to promote progenitor cell
growth. The direct synergistic effect of IL- 1 alpha on CSF-1-induced
progenitor growth was observed in all progenitor populations examined
(Lin-, Lin-Thy-1+, and Lin-Thy-1-) and was inhibited by MoAb 35F5. However,
the direct synergistic effect of IL-1 alpha on GM-CSF-responsive
progenitors. Lin- and Lin-Thy-1+, was partially inhibited by MoAb 35F5. In
contrast, the MoAb antitype II IL- 1R (MoAb 4E2) could not inhibit the
direct synergistic effects of IL-1 alpha on CSF-1- or GM-CSF-induced
progenitor growth. Thus, IL-1 alpha directly and indirectly stimulates the
growth and differentiation of purified progenitors through the type I IL-1R
but not the type II IL-1R.
Volume 84,
Issue 1,
pp. 125-132,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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