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 and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon-gamma (IFN-gamma), or IFN-gamma plus lipopolysaccharide. 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 inhibitor of L-arginine completely inhibited the killing activity of actitvated PM, while reconstitution of arginine-free medium with L-arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNI) play an important role in the mechanism. An oxygen-mediated mechanism didnot appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo.