Synergistic effect of liposomes and endotoxins on the activation of rat macrophage tumoricidal activity.

Macrophage biological responses to endotoxins have been extensively studied; nevertheless, the mechanisms by which endotoxins activate macrophage tumoricidal activity are not currently understood. We used liposomes to investigate the interaction of endotoxins with macrophages. In a medium containing 10 micrograms endotoxin/ml, macrophage-mediated cytolysis ranged from -7 to 36%. In all the experiments, 1mM dipalmitoyl phosphatidyl choline (DPPC) small unilamellar liposomes significantly induced or enhanced cytolysis, ranging from 30-90%. Liposomes and endotoxins had a synergistic effect on the macrophage cytolytic activity. This effect was dose-dependent on liposome concentration, ranging from 0.25-1 mM or 2 mM. Liposomes decreased the endotoxin concentration threshold necessary to induce cytolysis. They did not modify the kinetics of macrophage activation. Liposomes did not modify the binding of tumor cells to macrophages. The optimum synergistic effect was obtained when liposomes were present during the first 18 h of the mixed culture of macrophages and target cells, before adding endotoxins for the next 18 h. When cholesterol was added to DPPC (M/M), liposomes did not enhance but rather inhibited macrophage activation by endotoxins.