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The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors

(1998) JOURNAL OF IMMUNOLOGY. 160(4). p.1949-1956
Author
Organization
Abstract
The TNF-alpha-inducing capacity of different trypanosome components was analyzed in vitro, using as indicator cells a macrophage cell line (2C11/12) or peritoneal exudate cells from LPS-resistant C3H/HeJ mice and LPS-sensitive C3H/HeN mite. The variant-specific surface glycoprotein (VSG) was identified as the major TNF-alpha-inducing component present in trypanosome-soluble extracts. Both soluble (sVSG) and membrane-bound VSG (mfVSG) were shown to manifest similar TNF-alpha-inducing capacities, indicating that the dimyristoylglycerol (DMG) compound of the mfVSG anchor was not required for TNF-alpha triggering. Detailed analysis indicated that the glycosyl-inositol-phosphate (GIP) moiety was responsible for the TNF-alpha-inducing activity of VSG and that the presence of the GIP-associatcd galactose side chain was essential for optimal TNF-alpha production. Furthermore, the results showed that the responsiveness of macrophages toward the TNF-alpha-inducing activity of VSG was strictly dependent on the activation state of the macrophages, since resident macrophages required IFN-gamma preactivation to become responsive, Comparative analysis of the ability of both forms of VSG to activate macrophages revealed that mfVSG but not sVSG stimulates macrophages toward IL-1 alpha secretion and acquisition of LPS responsiveness. The priming activity of mfVSG toward LPS responsiveness was also demonstrated in vivo and may be relevant during trypanosome infections, since Trypanosoma brucei-infected mice became gradually LPS-hypersensitive during the course of infection. Collectively, the VSG of trypanosomes encompasses two distinct macrophage-activating components: while the GIP moiety of sVSG mediates TNF-alpha induction, the DMG compound of the mfVSG anchor contributes to IL-1 alpha induction and LPS sensitization.
Keywords
TUMOR-NECROSIS-FACTOR, GAMMA-INTERFERON, SIGNAL-TRANSDUCTION, ACTIVE INVOLVEMENT, FACTOR CACHECTIN, FACTOR INDUCTION, PHOSPHOLIPASE-C, GENE-EXPRESSION, PROTECTIVE ROLE, BRUCEI-BRUCEI

Citation

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Chicago
Magez, Stefan, B Stijlemans, Magdalena Radwanska, E Pays, MAJ Ferguson, and P De Baetselier. 1998. “The Glycosyl-inositol-phosphate and Dimyristoylglycerol Moieties of the Glycosylphosphatidylinositol Anchor of the Trypanosome Variant-specific Surface Glycoprotein Are Distinct Macrophage-activating Factors.” Journal of Immunology 160 (4): 1949–1956.
APA
Magez, S., Stijlemans, B., Radwanska, M., Pays, E., Ferguson, M., & De Baetselier, P. (1998). The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors. JOURNAL OF IMMUNOLOGY, 160(4), 1949–1956.
Vancouver
1.
Magez S, Stijlemans B, Radwanska M, Pays E, Ferguson M, De Baetselier P. The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors. JOURNAL OF IMMUNOLOGY. 1998;160(4):1949–56.
MLA
Magez, Stefan et al. “The Glycosyl-inositol-phosphate and Dimyristoylglycerol Moieties of the Glycosylphosphatidylinositol Anchor of the Trypanosome Variant-specific Surface Glycoprotein Are Distinct Macrophage-activating Factors.” JOURNAL OF IMMUNOLOGY 160.4 (1998): 1949–1956. Print.
@article{8572082,
  abstract     = {The TNF-alpha-inducing capacity of different trypanosome components was analyzed in vitro, using as indicator cells a macrophage cell line (2C11/12) or peritoneal exudate cells from LPS-resistant C3H/HeJ mice and LPS-sensitive C3H/HeN mite. The variant-specific surface glycoprotein (VSG) was identified as the major TNF-alpha-inducing component present in trypanosome-soluble extracts. Both soluble (sVSG) and membrane-bound VSG (mfVSG) were shown to manifest similar TNF-alpha-inducing capacities, indicating that the dimyristoylglycerol (DMG) compound of the mfVSG anchor was not required for TNF-alpha triggering. Detailed analysis indicated that the glycosyl-inositol-phosphate (GIP) moiety was responsible for the TNF-alpha-inducing activity of VSG and that the presence of the GIP-associatcd galactose side chain was essential for optimal TNF-alpha production. Furthermore, the results showed that the responsiveness of macrophages toward the TNF-alpha-inducing activity of VSG was strictly dependent on the activation state of the macrophages, since resident macrophages required IFN-gamma preactivation to become responsive, Comparative analysis of the ability of both forms of VSG to activate macrophages revealed that mfVSG but not sVSG stimulates macrophages toward IL-1 alpha secretion and acquisition of LPS responsiveness. The priming activity of mfVSG toward LPS responsiveness was also demonstrated in vivo and may be relevant during trypanosome infections, since Trypanosoma brucei-infected mice became gradually LPS-hypersensitive during the course of infection. Collectively, the VSG of trypanosomes encompasses two distinct macrophage-activating components: while the GIP moiety of sVSG mediates TNF-alpha induction, the DMG compound of the mfVSG anchor contributes to IL-1 alpha induction and LPS sensitization.},
  author       = {Magez, Stefan and Stijlemans, B and Radwanska, Magdalena and Pays, E and Ferguson, MAJ and De Baetselier, P},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  language     = {eng},
  number       = {4},
  pages        = {1949--1956},
  title        = {The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors},
  volume       = {160},
  year         = {1998},
}

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