Synergistic stimulation of macrophage proliferation by the monokines tumor
necrosis factor-alpha and colony-stimulating factor 1
DR Branch, AR Turner and LJ Guilbert
Department of Immunology, University of Alberta, Edmonton, Canada.
The effects of pure recombinant human tumor necrosis factor-alpha (TNF) on
the CSF-1-stimulated proliferation of well-defined populations of murine
macrophages are examined. Primary bone marrow-derived macrophages (BMM)
from endotoxin-resistant C3H/HeJ mice were characterized for homogeneity in
comparison with a cloned, growth factor-dependent macrophage cell line (S1)
also derived from C3H/HeJ bone marrow cells. The mitogenic effects of each
factor, alone and in combination, on the proliferation of both macrophage
populations over a two-day culture period were studied. In contrast to
CSF-1, TNF alone only slightly stimulated macrophage proliferation.
However, the combination of CSF-1 and TNF stimulated proliferation of both
primary BMM and S1 cells 1.5- to 2-fold greater than the sum of their
predicted individual contributions. Such synergy was observed even at very
high (plateau) levels of factors. TNF was found to transiently
down-regulate CSF-1 receptor levels on both populations. Down-regulation
was maximal at one hour; however, receptor numbers returned to initial, or
greater, levels after 24 hours of incubation. Thus, TNF, an inducible
monokine, greatly enhances the maximal mitogenic effects of CSF-1, an
inducer of TNF production. These observations suggest an autocrine rule for
TNF that involves synergy with (and perhaps obligatory cooperation with)
CSF-1 in the regulation of macrophage proliferation.
Volume 73,
Issue 1,
pp. 307-311,
01/01/1989
Copyright © 1989 by The American Society of Hematology
