GLYCOCONJUGATES ISOLATED FROM TRYPANOSOMA-CRUZI BUT NOT FROM LEISHMANIA SPECIES MEMBRANES TRIGGER NITRIC-OXIDE SYNTHESIS AS WELL AS MICROBICIDAL ACTIVITY IN IFN-GAMMA-PRIMED MACROPHAGES

In the present study, we investigated the role of glycosylphosphatidyl inositol-anchored mucin-like glycoproteins (GPI-mucins) from Trypanoso ma cruzi trypomastigotes in triggering the synthesis of nitric oxide a s well as the microbicidal activity in murine macrophages. Our results show that CPI-mucins isolated from trypomastigote membranes are poten t inducers of nitric oxide synthesis by IFN-gamma-primed macrophages, even at concentrations as low as 10 ng/ml. Our data also indicate the important role of glycosylphosphatidylinositol anchors from GPI-mucins as the second signal responsible for induction of nitric oxide synthe sis by macrophages. To further investigate the role of these parasite molecules in inducing parasiticidal function, we cultured macrophages in the presence or absence of trypomastigote GPI-mucins and/or IFN-gam ma and then infected these cells with either Leishmania spp. or T. cru zi. IFN-gamma was sufficient to induce microbial activity in macrophag es infected with T. cruzi trypomastigotes. In contrast, killing of dif ferent species of Leishmania was further enhanced when macrophages exp osed to IFN-gamma were also costimulated with trypomastigote-derived C PI-mucins. Our results also indicate that different glycolipids obtain ed from Leishmania major or Leishmania donovani (i.e., lipophosphoglyc ans or glycoinositolphospholipids) were unable to potentiate nitric ox ide synthesis and/or microbicidal activity displayed by IFN-gamma-prim ed macrophages.