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Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid
phosphatase-positive osteoclast-like multinucleated giant cells from human
monocytes
KS Akagawa, N Takasuka, Y Nozaki, I Komuro, M Azuma, M Ueda, M Naito and K Takahashi
Department of Immunology, National Institute of Health, Tokyo, Japan.
We previously showed that granulocyte-macrophage colony-stimulating factor
(GM-CSF) and macrophage colony-stimulating factor (M-CSF) stimulate the
differentiation of human monocytes into two phenotypically distinct types
of macrophages. However, in vivo, not only CSF but also many other
cytokines are produced under various conditions. Those cytokines may
modulate the differentiation of monocytes by CSFs. In the present study, we
showed that CD14+ adherent human monocytes can differentiate into CD1+relB+
dendritic cells (DC) by the combination of GM-CSF plus interleukin-4 (IL-4)
and that they differentiate into tartrate-resistant acid phosphatase
(TRAP)-positive osteoclast-like multinucleated giant cells (MGC) by the
combination of M-CSF plus IL-4. However, the monocyte-derived DC were not
terminally differentiated cells; they could still convert to macrophages in
response to M-CSF. Tumor necrosis factor-alpha (TNF-alpha) stimulated the
terminal differentiation of the DC by downregulating the expression of the
M-CSF receptor, cfms mRNA, and aborting the potential to convert to
macrophages. In contrast to IL-4, interferon-gamma (IFN-gamma) had no
demonstrable effect on the differentiation of monocytes. Rather, IFN- gamma
antagonized the effect of IL-4 and suppressed the DC and MGC formation
induced by GM-CSF + IL-4 and M-CSF + IL-4, respectively. Taken together,
these results provide a new aspect to our knowledge of monocyte
differentiation and provide evidence that human monocytes are flexible in
their differentiation potential and are precursors not only of macrophages
but also of CD1+relB+DC and TRAP-positive MGC. Such a diverse pathway of
monocyte differentiation may constitute one of the basic mechanisms of
immune regulation.
Volume 88,
Issue 10,
pp. 4029-4039,
11/15/1996
Copyright © 1996 by The American Society of Hematology
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3245 - 3287.
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I. Komuro, N. Keicho, A. Iwamoto, and K. S. Akagawa
Human Alveolar Macrophages and Granulocyte-macrophage Colony-stimulating Factor-induced Monocyte-derived Macrophages Are Resistant to H2O2 via Their High Basal and Inducible Levels of Catalase Activity
J. Biol. Chem.,
June 22, 2001;
276(26):
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[Abstract]
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