Mak N K, Leung K N, Fung M C, Hapel A J
Experimental Haematology Group, John Curtin School of Medical Research, Australian National University, Canberra.
Immunobiology. 1994 Feb;190(1-2):1-12. doi: 10.1016/s0171-2985(11)80279-2.
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.
我们已经证明，百日咳毒素（PTx）可在体外调节肿瘤坏死因子-α（TNF-α）诱导WEHI-3B（JCS）髓系白血病细胞单核细胞分化的作用。单独的PTx（0.1 - 2 ng/ml）无细胞毒性，且不会诱导JCS细胞发生形态变化。然而，在次优浓度的TNF-α（25 U/ml）存在的情况下，PTx（1 ng/ml）协同发挥作用，抑制JCS细胞增殖并诱导其单核细胞分化。PTx与TNF-α联合可增加JCS细胞上巨噬细胞分化标志物（Mac-1）的表达，细胞的吞噬活性也得到增强。此外，经PTx和TNF-α处理的JCS细胞在体内的致瘤能力降低。数据表明，一种对PTx敏感的G蛋白可能参与调节TNF-α诱导的髓系白血病JCS细胞单核细胞分化，并且PTx与TNF-α联合可能对某些形式的骨髓单核细胞白血病的治疗有用。
