PMID- 12815041
OWN - NLM
STAT- MEDLINE
DCOM- 20031002
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 35
DP  - 2003 Aug 29
TI  - Roles of glycosylphosphatidylinositols of Toxoplasma gondii. Induction of tumor 
      necrosis factor-alpha production in macrophages.
PG  - 32987-93
AB  - Toxoplasma gondii is a ubiquitous parasitic protozoan, which causes congenital 
      infectious diseases as well as severe encephalitis, a major cause of death among 
      immune-deficient persons, such as AIDS patients. T. gondii is normally controlled 
      by the immune system of healthy individuals, leading to an asymptomatic 
      infection. T. gondii triggers early cytokine production, which, to a certain 
      extent, protects the host against replication of tachyzoites, the infective form 
      of the parasite. Glycosylphosphatidylinositols (GPIs) constitute a class of 
      glycolipids that have various functions, the most fundamental being to link 
      proteins to eucaryotic cell membranes. GPIs are involved in the pathogenicity of 
      other protozoan parasites and are known to induce tumor necrosis factor-alpha 
      (TNF alpha) production. We show that GPIs highly purified from T. gondii 
      tachyzoites, as well as their core glycans, induce TNF alpha production in 
      macrophages. A chemically synthesized GPI of T. gondii lacking its lipid moiety, 
      GPIa, has the same effect as the natural GPIs, whereas a chemically synthesized 
      molecule with dialkylglycerol instead of diacylglycerol as lipid moiety, GPIb, 
      does not induce TNF alpha production. Moreover, GPIb inhibits the TNF alpha 
      production induced by T. gondii GPI or by GPIa. The core glycan prepared from the 
      two chemically synthesized molecules activates macrophages, showing that the 
      lipid moiety may regulate signaling. Stimulation of macrophages with GPIs of T. 
      gondii results in activation of the transcription factor NF-kappa B, which is 
      inhibited by the chemically synthesized GPIb, suggesting the involvement of 
      NF-kappa B in TNF alpha gene expression. Our results support the idea that T. 
      gondii GPIs are bioactive factors that participate in the production of TNF alpha 
      during toxoplasmal pathogenesis.
FAU - Debierre-Grockiego, Francoise
AU  - Debierre-Grockiego F
AD  - Institute for Virology, Medical Center for Hygiene, Philipps University, 
      Robert-Koch-Strasse 17, D-35037 Marburg, Germany. debierre@mailer.uni-marburg.de
FAU - Azzouz, Nahid
AU  - Azzouz N
FAU - Schmidt, Jorg
AU  - Schmidt J
FAU - Dubremetz, Jean-Francois
AU  - Dubremetz JF
FAU - Geyer, Hildegard
AU  - Geyer H
FAU - Geyer, Rudolf
AU  - Geyer R
FAU - Weingart, Ralf
AU  - Weingart R
FAU - Schmidt, Richard R
AU  - Schmidt RR
FAU - Schwarz, Ralph T
AU  - Schwarz RT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030618
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Diglycerides)
RN  - 0 (Glycolipids)
RN  - 0 (Glycosylphosphatidylinositols)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Carbohydrate Sequence
MH  - Cell Membrane/metabolism
MH  - Chlorocebus aethiops
MH  - Chromatography, Thin Layer
MH  - Diglycerides/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glycolipids/metabolism
MH  - Glycosylphosphatidylinositols/*chemistry/*physiology
MH  - Lipid Metabolism
MH  - Macrophage Activation
MH  - Macrophages/*metabolism/*parasitology
MH  - Mice
MH  - Models, Chemical
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - Time Factors
MH  - Toxoplasma/*metabolism/*pathogenicity
MH  - Transcription Factor RelA
MH  - Transcription Factors/metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
MH  - Vero Cells
EDAT- 2003/06/20 05:00
MHDA- 2003/10/03 05:00
CRDT- 2003/06/20 05:00
PHST- 2003/06/20 05:00 [pubmed]
PHST- 2003/10/03 05:00 [medline]
PHST- 2003/06/20 05:00 [entrez]
AID - S0021-9258(20)83858-7 [pii]
AID - 10.1074/jbc.M304791200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Aug 29;278(35):32987-93. doi: 10.1074/jbc.M304791200. Epub 2003 
      Jun 18.