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Direct Macrophage Activation by TNF-
to Osteoclastic or Cytocidal Phenotype1
Department of Experimental Pathology, St. George’s Hospital Medical School, London, United Kingdom
TNF-related activation-induced cytokine (TRANCE; also called
receptor activator of NF-
B ligand (RANKL), osteoclast
differentiation factor (ODF), osteoprotegerin ligand (OPGL), and
TNFSF11) induces the differentiation of progenitors of the mononuclear
phagocyte lineage into osteoclasts in the presence of M-CSF.
Surprisingly, in view of its potent ability to induce inflammation and
activate macrophage cytocidal function, TNF-
has also been found to
induce osteoclast-like cells in vitro under similar conditions. This
raises questions concerning both the nature of osteoclasts and the
mechanism of lineage choice in mononuclear phagocytes. We found that,
as with TRANCE, the macrophage deactivator TGF-ß1
strongly promoted TNF--induced osteoclast-like cell formation from
immature bone marrow macrophages. This was abolished by IFN-
.
However, TRANCE did not share the ability of TNF- to activate NO
production or heighten respiratory burst potential by macrophages, or
induce inflammation on s.c. injection into mice. This suggests that
TGF-ß1 promotes osteoclast formation not only by
inhibiting cytocidal behavior, but also by actively directing TNF-
activation of precursors toward osteoclasts. The osteoclast appears to
be an equivalent, alternative destiny for precursors to that of
cytocidal macrophage, and may represent an activated variant of
scavenger macrophage.
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