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Peptide growth factors stimulate macrophage colony-stimulating factor in
murine stromal cells
SL Abboud and M Pinzani
Department of Pathology, Veterans Administration Medical Center, Cleveland,
OH.
Bone marrow stromal cells influence hematopoiesis through cell-cell
interaction and release of hematopoietic growth factors. Macrophage
colony-stimulating factor (M-CSF) is constitutively produced by several
murine and human stromal cell lines and is induced by inflammatory
mediators such as interleukin-1 alpha or tumor necrosis factor-alpha
(TNF-alpha) in a variety of mesenchymal cells. Other potentially important
regulatory molecules such as platelet-derived growth factor (PDGF) and
basic fibroblast growth factor (bFGF), released by activated monocytes in
response to inflammation, stimulate the growth of human stromal cells.
However, the effect of these peptide mitogens on M-CSF expression in
stromal cells has not been explored. In this study, we used TC-1 murine
bone marrow-derived stromal cells that constitutively secrete M-CSF to
determine the effect of PDGF and bFGF on cell proliferation and M-CSF gene
expression. PDGF and bFGF, but not TNF- alpha, were potent mitogens for the
TC-1 cells. Similar to mouse L cells, TC-1 murine stromal cells
constitutively expressed two major mRNA transcripts of 4.4 and 2.2 kb that
hybridized to a murine M-CSF cDNA. PDGF, bFGF, and TNF-alpha markedly
stimulated the steady-state expression of M-CSF mRNA with different
time-course kinetics. The increased expression of M-CSF mRNA was associated
with enhanced secretion of M-CSF as determined by radioimmunoassay. These
findings suggest that PDGF, bFGF, and TNF-alpha may regulate hematopoiesis
indirectly through release of M-CSF by stromal cells and may modulate, at
least in part, the hematopoietic response to inflammation.
Volume 78,
Issue 1,
pp. 103-109,
07/01/1991
Copyright © 1991 by The American Society of Hematology
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