Augmentation of tumor necrosis factor-alpha-induced monocytic differentiation of a myelomonocytic leukemia (WEHI-3B JCS) by pertussis toxin.

We have shown that pertussis toxin (PTx) modulates the effect of tumor necrosis factor-alpha (TNF-alpha) in inducing monocytic differentiation of WEHI-3B (JCS) myeloid leukemic cells in vitro. PTx (0.1-2 ng/ml) alone was not cytotoxic and did not induce morphological changes in JCS cells. In the presence of a suboptimal concentration of TNF-alpha (25 U/ml), however, PTx (1 ng/ml) acted synergistically in inhibiting proliferation and in inducing monocytic differentiation of the JCS cells. Expression of the macrophage differentiation marker (Mac-1) on JCS cells was increased by the combination of PTx and TNF-alpha, and phagocytic activity of the cells was also enhanced. Moreover, JCS cells treated with PTx and TNF-alpha had reduced tumorigenic capacity in vivo. The data suggest that a PTx-sensitive G protein may be involved in regulating the TNF-alpha-induced monocytic differentiation of the myeloid leukemic JCS cells and that combination of PTx and TNF-alpha may be useful in the treatment of some forms of myelomonocytic leukemia.