Monocytic differentiation of a myelomonocytic leukemic cell (WEHI 3B JCS) is induced by tumour necrosis factor-alpha (TNF-alpha).
We have isolated a subclone (JCS) of the WEHI 3B myelomonocytic leukemia, which acquires the characteristics of mature macrophage lineage cells in the presence of PMA or noncytotoxic concentrations of TNF-alpha (600-1200 U/ml). JCS cells were compared with D+ and D- subclones of WEHI 3B. Unlike D+ cells, JCS cells did not produce differentiated granulocyte-macrophage colonies in the presence of postendotoxin serum or recombinant G-CSF. Stimulation with PMA or TNF-alpha reduced proliferation of JCS cells. TNF-alpha decreased the level of cell surface J11D antigen with concurrent increased expression of Mac-1 and FcR antigens and phagocytic activity. These TNF-alpha-mediated effects were enhanced by addition of IFN-gamma to the cultures. Furthermore, differentiation-inducing activity of PMA could be prevented using neutralizing anti-TNF-alpha antibodies. The results indicate that exogenous TNF-alpha can act as a differentiative agent for JCS cells and that endogenous TNF-alpha is the active substance when PMA is used to stimulate macrophage differentiation of JCS cells.
Mak
N K
NK
Experimental Haematology Group, John Curtin School of Medical Research, Australian National University, Canberra.
Fung
M C
MC
Leung
K N
KN
Hapel
A J
AJ
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology*; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D010587:Phagocytosis; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015214:Antigens, Differentiation, Myelomonocytic; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate