Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages

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dc.contributor.authorCamargo, M. M.
dc.contributor.authorAlmeida, I. C.
dc.contributor.authorPereira, MES
dc.contributor.authorFerguson, MAJ
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.authorGazzinelli, R. T.
dc.contributor.institutionCTR PESQUISAS RENE RACHOU FIOCRUZ
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUNIV DUNDEE
dc.date.accessioned2018-06-15T18:02:25Z
dc.date.available2018-06-15T18:02:25Z
dc.date.issued1997-06-15
dc.description.abstractComponents of Trypanosoma cruzi able to induce the production of IL-12 and other proinflammatory cytokines by macrophages were identified, Murine inflammatory macrophages were cultured with live parasites or with cellular components from different developmental forms of T. cruzi (i.e., trypomastigotes, amastigotes, metacyclic trypomastigotes, and epimastigotes), and the cytokine levels were measured after 24 and 48 h. Our results indicate that live trypomastigotes or live amastigotes (but not five epimastigotes or live metacyclic trypomastigotes) as well as trypomastigote extracts (but not extracts derived from epimastigotes) induce IL-12 and TNF-alpha synthesis by macrophages. Such biological activity is enhanced in membrane preparations from trypomastigotes, Further enrichment of the trypomastigote-derived monokine-inducing factor was obtained by solvent extraction and hydrophobic-interaction chromatography, The resultant purified molecules are a family of closely related glycoconjugates with predominant species at 70 to 80 and 120 to 200 kDa. These molecules are composed of carbohydrate chains O-linked to a polypeptide backbone that is anchored to the trypomastigote membrane via a glycosylphosphatidylinositol structure. The trypomastigote-derived glycoconjugates are active in inducing cytokine synthesis by macrophages at concentrations of 100 ng/ml. These effects are highly potentiated by IFN-gamma. Mapping of the glycoconjugate molecules to characterize the structural requirements for macrophage activation suggested that nonsaturated acyl fatty acid chains and periodate-sensitive units from the glycosylphosphatidylinositol anchor are important elements for the infective trypomastigote form to initiate cytokine synthesis by macrophages.en
dc.description.affiliationCTR PESQUISAS RENE RACHOU FIOCRUZ,LAB CHAGAS DIS,FIOCRUZ,BR-30190002 BELO HORIZONT,MG,BRAZIL
dc.description.affiliationUNIV FED MINAS GERAIS,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL
dc.description.affiliationUNIV FED SAO PAULO,DISCIPLINE CELL BIOL,SAO PAULO,BRAZIL
dc.description.affiliationUNIV DUNDEE,DEPT BIOCHEM,DUNDEE DD1 4HN,SCOTLAND
dc.description.affiliationUnifespUNIV FED SAO PAULO,DISCIPLINE CELL BIOL,SAO PAULO,BRAZIL
dc.description.sourceWeb of Science
dc.format.extent5890-5901
dc.identifierhttp://www.jimmunol.org/content/158/12/5890
dc.identifier.citationJournal Of Immunology. Bethesda: Amer Assoc Immunologists, v. 158, n. 12, p. 5890-5901, 1997.
dc.identifier.issn0022-1767
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/44409
dc.identifier.wosWOS:A1997XE74900040
dc.language.isoeng
dc.publisherAmer Assoc Immunologists
dc.relation.ispartofJournal Of Immunology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.titleGlycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophagesen
dc.typeinfo:eu-repo/semantics/article
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