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PMID: 10747016 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents.

The EMBO journal ·Vol. 19 ·No. 7 ·2000-04-03 ·Pages 1476-85

Almeida IC, Camargo MM, Procópio DO, Silva LS, Mehlert A, Travassos LR, Gazzinelli RT, Ferguson MA

Abstract

Intracellular protozoan parasites are potent stimulators of cell-mediated immunity. The induction of macrophage proinflammatory cytokines by Trypanosoma cruzi is considered to be important in controlling the infection and the outcome of Chagas' disease. Here we show that the potent tumour necrosis factor-alpha-, interleukin-12- and nitric oxide-inducing activities of T.cruzi trypomastigote mucins were recovered quantitatively in a highly purified and characterized glycosylphosphatidylinositol (GPI) anchor fraction of this material. The bioactive trypomastigote GPI fraction was compared with a relatively inactive GPI fraction prepared from T. cruzi epimastigote mucins. The trypomastigote GPI structures were found to contain additional galactose residues and unsaturated, instead of saturated, fatty acids in the sn-2 position of the alkylacylglycerolipid component. The latter feature is essential for the extreme potency of the trypomastigote GPI fraction, which is at least as active as bacterial endotoxin and Mycoplasma lipopeptide and, therefore, one of the most potent microbial proinflammatory agents known.

MeSH Terms
Amino Acid Sequence Animals Carbohydrate Sequence Chagas Disease/immunology Glycosylphosphatidylinositols/chemistry,isolation & purification,pharmacology In Vitro Techniques Inflammation Mediators/chemistry,isolation & purification,pharmacology Interleukin-12/biosynthesis Macrophages, Peritoneal/drug effects,immunology,metabolism Male Mice Mice, Inbred C3H Molecular Sequence Data Mucins/chemistry,isolation & purification,pharmacology Nitric Oxide/biosynthesis Trypanosoma cruzi/chemistry,immunology,pathogenicity Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Glycosylphosphatidylinositols Inflammation Mediators Mucins Tumor Necrosis Factor-alpha Interleukin-12 Nitric Oxide
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Almeida I C
Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK.
Camargo M M
Procópio D O
Silva L S
Mehlert A
Travassos L R
Gazzinelli R T
Ferguson M A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.7.1476
Published
2000-04-03
Pages
1476-85
Language
English
Region
England
NLM ID
8208664
PMCID
PMC310217
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.7.1476 PMC Full Text View journal details
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