Recombinant tumor necrosis factor enhances the proliferative responsiveness
of murine peripheral macrophages to macrophage colony- stimulating factor
but inhibits their proliferative responsiveness to granulocyte-macrophage
colony-stimulating factor
BD Chen and M Mueller
Department of Internal Medicine, Wayne State University School of Medicine,
Detroit, Michigan 48201.
Tumor necrosis factor (TNF) is a protein produced by activated macrophages
in response to endotoxin. The effect of recombinant murine TNF (rMuTNF) on
the growth of murine tissue-derived macrophage colony- forming units
(CFU-M) which are responsive to both macrophage and granulocyte-macrophage
colony-stimulating factors (M-CSF and GM-CSF), was studied. TNF alone did
not stimulate macrophage proliferation but did prolong their survival in
vitro. The proliferative response of CFU- M to M-CSF, however, was greatly
enhanced by the presence of TNF. The enhancement effect of TNF is
dose-dependent, reaching a maximum at approximately 50 U/mL. In contrast,
the proliferative responsiveness of CFU-M to GM-CSF was inhibited by the
concurrent addition of rMuTNF. Both effects appear to be caused directly by
rMuTNF, rather than by the secondary factor(s) produced by TNF-treated
macrophages. TNF treatment also induced a transient downmodulation of M-CSF
receptors in cultured macrophages and accelerated their uptake and use of
exogenous M-CSF, which may account for, at least in part, the enhanced
proliferative activity in response to M-CSF. Short-term treatment (24
hours) was not sufficient to induce either an enhancing or an inhibitory
effect upon CFU-M. This study suggests an autoregulatory role for TNF in
the production of mature tissue macrophages by selectively enhancing their
proliferative response to lineage specific growth factor, M-CSF.
Volume 75,
Issue 8,
pp. 1627-1632,
04/15/1990
Copyright © 1990 by The American Society of Hematology
