Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages
Camargo, M.M.; Almeida, I.C.; Pereira, M.E.; Ferguson, M.A.; Travassos, L.R.; Gazzinelli, R.T.
Journal of Immunology 158(12): 5890-5901
1997
ISSN/ISBN: 0022-1767 PMID: 9190942 Document Number: 474712
Murine inflammatory macrophages were cultured with live Trypanosoma cruzi (Y strain) parasites or with cellular components from trypomastigotes, amastigotes, metacyclic trypomastigotes or epimastigotes, and the cytokine levels were measured after 24 and 48 h. Live trypomastigotes or amastigotes (but not the other 2 stages) induced the macrophages to synthesize interleukin-12 (IL-12) and tumour necrosis factor alpha (TNF- alpha ), as did trypomastigote (but not epimastigote) extracts, particularly membrane preparations. The molecules responsible were purified and found to be a family of glycoconjugates, anchored to the cell membrane by a glycosylphosphatidylinositol structure, with predominant species at 70 to 80 and 120 to 200 kDa. They induced synthesis of IL-12, TNF- alpha and other cytokines by macrophages at concentrations of about 100 ng/ml (higher concentrations tended to be less effective); induction was highly potentiated by IFN- gamma . Mapping of the glycoconjugate molecules suggested that nonsaturated acyl fatty acid chains and periodate-sensitive units from the glycosylphosphatidylinositol anchor are important for the trypomastigote to initiate cytokine synthesis by macrophages.