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SE Jacobsen, FW Ruscetti, CM Dubois, J Wine and JR Keller
Laboratory of Molecular Immunoregulation, National Cancer Institute-
Frederick Cancer Research and Development Center, MD 21702-1201.
In many cells systems, the cellular interaction between two or more humoral
factors leads to a synergistic response in terms of cellular growth and
function. In particular, the growth and differentiation of hematopoietic
progenitor cells involves numerous synergistic interactions between
colony-stimulating factors (CSFs) that individually stimulate hematopoiesis
(granulocyte-CSF, granulocyte- macrophage-CSF, and interleukin-3 [IL-3]),
as well as between these factors and other cytokines that individually have
no proliferative effect on progenitor cell growth (IL-1 and IL-6). The
present study investigated whether hematopoietic growth factor (HGF)
synergy could be mediated by upregulation of CSF receptors. Synergistic
effects on bone marrow (BM) progenitor cell colony formation, regardless of
the combination of factors used, were consistently preceded by increased
CSF receptor expression on highly enriched BM progenitor cells, but not on
unfractionated BM cells. Induction of CSF receptors preceded detectable
differentiation and did not require cell division because nocodazole, an
inhibitor of mitosis, blocked CSF-mediated cell proliferation, but not
receptor upregulation. Furthermore, combinations of cytokines that did not
synergize also failed to affect the level of CSF receptors on BM
progenitors. These results have led us to propose a model for HGF synergy
whereby one mechanism of action the investigated synergistic cytokines
might be the ability to induce increased expression of CSF receptors.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
