Tumor Necrosis Factor Changes Sensitivity of Differentiation of Mouse Leukemia M1 Cells by Lipopolysaccharide

A clone of mouse leukemia M1 cells was induced to differentiate by lipopolysaccharide (LPS) (LPS-sensitive clone) while another clone of the same cells was resistant (LPS-resistant clone). LPS and lipid A preparations from Pseudomonas diminuta and Pseudomonas vesicularis were as active as Escherichia coli LPS in the induction of differentiation of the LPS-sensitive clone. Synthetic lipid A precursor Ia (compound 406), which has no interleukin 1 (IL-1)-inducing activity toward monocytes, had strong differentiation-inducing activity toward the LPS-sensitive clone. The combined treatment of the LPS-sensitive clone with LPS and recombinant tumor necrosis factor (rTNF) did not further increase the degree of differentiation induced by LPS alone. By contrast, the LPS-resistant clone was markedly induced to differentiate by LPS in the presence of rTNF. Combined treatment of the LPS-resistant clone with LPS and other cytokines such as recombinant IL-1α, recombinant granulocyte colony-stimulating factor, and interferon-γ was not effective in inducing marked synergistic differentiation. These results raise the possibility that rTNF changes the sensitivity of M1 cells to induction of differentiation by LPS.