Monocytic Differentiation of a Myelomonocytic Leukemic Cell (WEHI 3B JCS) Is Induced by Tumour Necrosis Factor-Alpha (TNF-α)

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-α(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-α reduced proliferation of JCS cells. TNF-α decreased the level of cell surface J11D antigen with concurrent increased expression of Mac-1 and FcR antigens and phagocylic activity. These TNF-α-mediated effects were enhanced by addition of IFN-γ to the cultures. Furthermore, differentiation-inducing activity of PMA could be prevented using neutralizing anti-TNF-α antibodies. The results indicate that exogenous TNF-α can act as a differentiative agent for JCS cells and that endogenous TNF-α is the active substance when PMA is used to stimulate macrophage differentiation of JCS cells.