title: 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.
abstract: In the present study, we investigated the role of glycosylphosphatidylinositol-anchored mucin-like glycoproteins (GPI-mucins) from Trypanosoma cruzi trypomastigotes in triggering the synthesis of nitric oxide as well as the microbicidal activity in murine macrophages. Our results show that GPI-mucins isolated from trypomastigote membranes are potent 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 synthesis 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-gamma and then infected these cells with either Leishmania spp. or T. cruzi. IFN-gamma was sufficient to induce microbial activity in macrophages infected with T. cruzi trypomastigotes. In contrast, killing of different species of Leishmania was further enhanced when macrophages exposed to IFN-gamma were also costimulated with trypomastigote-derived GPI-mucins. Our results also indicate that different glycolipids obtained from Leishmania major or Leishmania donovani (i.e., lipophosphoglycans or glycoinositolphospholipids) were unable to potentiate nitric oxide synthesis and/or microbicidal activity displayed by IFN-gamma-primed macrophages.
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Camargo
authors.forename: A C
authors.initials: AC
authors.lastname: Andrade
authors.forename: I C
authors.initials: IC
authors.lastname: Almeida
authors.forename: L R
authors.initials: LR
authors.lastname: Travassos
authors.forename: R T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D017261:Glycosylphosphatidylinositols / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007739:L Cells; D007891:Leishmania / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009077:Mucins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000981:Antiprotozoal Agents; D017261:Glycosylphosphatidylinositols; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma