ARGININE-DEPENDENT GENERATION OF REACTIVE NITROGEN INTERMEDIATES IS INSTRUMENTAL IN THE IN-VITRO KILLING OF PROTOSCOLECES OF ECHINOCOCCUS-MULTILOCULARIS BY ACTIVATED MACROPHAGES

The interaction between protoscoleces of Echinococcus multilocularis a nd activated murine macrophages was examined in this study. Marked pro toscolicidal activity was displayed by peritoneal macrophages (PM) act ivated with interferon-gamma (IFN-gamma), or IFN-gamma plus lipopolysa ccharide. Pretreatment of the parasites with heat-inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. N(G)-monomethyl-L-arginine, a competitive i nhibitor of L-arginine completely inhibited the killing activity of ac titvated PM, while reconstitution of arginine-free medium with L-argin ine restored the killing properties of the activated PM. The results s how that activated PM have the ability to kill E. multilocularis proto scoleces in vitro and suggest that reactive nitrogen intermediates (RN I) play an important role in the mechanism. An oxygen-mediated mechani sm didnot appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent ki lling mechanism was enhanced by superoxide dismutase (SOD), probably b ecause SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preve nting of the dissemination of E. multilocularis infection in vivo.