Synergistic generation of tumoricidal macrophages by muroctasin and interferon-gamma

The ability of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, to generate tumoricidal macrophages was investigated. MDP-Lys(L18) alone at the dose employed, 100 ng/ml, did not activate macrophages, and by combination with interferon-gamma (IFN-gamma), synergistically generated tumoricidal macrophages. Priming by IFN-gamma of macrophages enhanced endocytosis of MDP-Lys(L18) by the macrophages, which must be one of the mechanisms of the synergism. Thus, MDP-Lys(L18) is suggested to be a potent macrophage activator.