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Tumor necrosis factor-alpha- and interleukin-6-triggered mast cell
development from mouse spleen cells
ZQ Hu, K Kobayashi, N Zenda and T Shimamura
Department of Microbiology and Immunology, Showa University School of
Medicine, Tokyo, Japan.
We previously showed that interleukin-3 (IL-3) alone is not sufficient,
although it is essential for murine mucosal-type mast cell development and
that prostaglandin E (PGE) and interferon-gamma (IFN-gamma) are critical
for survival or differentiation of mast cell precursors. We also confirmed
that IL-4 is a key inhibitor for mast cell precursors despite being a
growth factor of mast cells. In the present work, mouse spleen cells were
cultured with recombinant (r) IL-1 beta, rIL-5, rIL- 6, rIL-9,
granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor
(SCF), tumor transforming growth factor-beta (TGF- beta), or tumor necrosis
factor-alpha (TNF-alpha) in the presence of endogenous IL-3. After 12 days
of culture, mast cell development was induced by rIL-6 and rTNF-alpha,
rIL-1 beta, rIL-5, rGM-CSF, rTGF-beta and even the mast cell growth
factors, rIL-9 and rSCF, failed to induce mast cell development. However,
unlike IL-9 and SCF, IL-6 and TNF-alpha did not promote the growth of mast
cells already developed. Macrophage may be one of the responsive cells of
IL-6 and TNF-alpha in the cultures, because removal of macrophages greatly
reduced the mast cell development induced by the cytokines. The actions of
TNF-alpha and IL-6 were inhibited by indomethacin, an inhibitor for
prostaglandin synthesis, and by neutralizing anti-IFN-gamma and anti-IL-3
antibodies. rIL-4, when added at the start of the culture, also inhibited
mast cell development induced by rIL-6 and rTNF-alpha. Nevertheless,
neutralizing anti-IL-6 and anti-TNF-alpha antibodies did not suppress mast
cell development induced by PGE and IFN-gamma. TNF-alpha and IL-6 enhanced
IFN-gamma production, but suppressed IL-4 production in the cultures. Mast
cell numbers induced were inversely and directly proportional to IL-4 and
IFN-gamma levels, respectively. These results indicate that inflammatory
mediators as triggers are important for mast cell development although they
are not the mast cell growth factors.
Volume 89,
Issue 2,
pp. 526-533,
01/15/1997
Copyright © 1997 by The American Society of Hematology

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