In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony-
stimulating factor receptor modulation
K Hestdal, SE Jacobsen, FW Ruscetti, CM Dubois, DL Longo, R Chizzonite, JJ Oppenheim and JR Keller
Biological Response Modifiers, Program Resources, Inc/DynCorp, Inc,
National Cancer Institute, Frederick Cancer Research and Development
Center, MD 21702-1201.
To determine the mechanism(s) by which interleukin-1 (IL-1) promotes
granulopoiesis in vivo, we examined the effect of in vivo administration of
IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone
marrow cells (BMCs) and whether this directly correlated with progenitor
cell responsiveness. Administration of IL-1 alpha to mice induced the
upregulation of both granulocyte- macrophage-CSF (GM-CSF) and IL-3
receptors, which reached a maximum 24 hours after IL-1 alpha injection on
unfractionated BMCs. This upregulation was more pronounced on the
progenitor-enriched cell population (lineage-negative [Lin(-)]). The
enhanced GM-CSF and IL-3 receptor expression directly correlated with
enhanced IL-3- or GM-CSF- induced growth of colony-forming unit-culture
(CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages,
granulocytes, and erythroid cells). In addition, the absolute number of
high proliferative potential-colony-forming cells (HPP-CFC) was increased
fivefold. In contrast, granulocyte-CSF (G-CSF)-specific binding on
unfractionated BMCs was rapidly (4 hours) reduced after IL-1 alpha
administration and returned to control levels by 24 hours. This reduction
correlated with IL-1 alpha-induced margination of mature granulocytes
(RBC-8C5hi cells), which express high levels of G-CSF receptors. IL-1 alpha
treatment did not affect G-CSF receptor expression on Lin- cells.
Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the
IL-1 alpha-induced upregulation of GM-CSF and IL-3 receptor expression on
BMCs. Taken together, as one possible mechanism, IL-1 alpha in vivo may
stimulate the expression of functional GM-CSF and IL- 3 receptors on BMCs
indirectly, and, in concert with the induction of circulating CSF levels,
may account for the ability of IL-1 alpha to stimulate hematopoiesis in
vivo.
Volume 80,
Issue 10,
pp. 2486-2494,
11/15/1992
Copyright © 1992 by The American Society of Hematology
