Induction of nitric oxide production by ganglioside GM3 in murine peritoneal macrophages activated for tumor cytotoxicity.

Recently, it was found that ganglioside GM3, known as a potent monocytic cell differentiation inducer, mimicked bacterial lipopolysaccharide (LPS) in the activation of macrophage-mediated tumor cytotoxicity (MTC). Since GM3 and LPS share partial structural and functional similarity, we postulate that the GM3-induced MTC was due to the induction of nitric oxide(NO) production in murine peritoneal macrophages (M phi s). MATERIALS RESULTS, CONCLUSIONS: Ganglioside GM3 was highly purified from canine erythrocytes by the authors. Murine peritoneal M phi s were used as the effector cells, and mouse ascites hepatoma cell line HCa-F25/16A3-F as the target cells. We found that: GM3 induced NO production by macrophages in a time- and dose-dependent manner; GM3 and IFN-gamma synergistically increased NO production; GM3 markedly enhanced MTC; both NO production and MTC were significantly inhibited by aminoguanidine. These results demonstrated for the first time that ganglioside GM3 in vitro induces the production of nitric oxide by macrophages, and the GM3-induced MTC is NO-dependent.