GLYCOSYLPHOSPHATIDYLINOSITOL TOXIN OF TRYPANOSOMA-BRUCEI REGULATES IL-1-ALPHA AND TNF-ALPHA EXPRESSION IN MACROPHAGES BY PROTEIN-TYROSINE KINASE MEDIATED SIGNAL-TRANSDUCTION
- Author(s)
- Tachado, SD; Schofield, L;
- Details
- Publication Year 1994-12-15,Volume 205,Issue #2,Page 984-991
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Publication Type
- Journal Article
- Abstract
- A purified, structurally defined glycosylphosphatidylinositol (GPI) derived from the Variant Surface Glycoprotein (VSG) of Trypanosoma brucei, and its biosynthetic precursor P2, was able at submicromolar concentrations to regulate cytokine expression when added directly as pharmacological agonist to host macrophages, by activation of an endogenous protein tyrosine-kinase (PTK) mediated signal transduction pathway. GPI induces rapid onset tyrosine phosphorylation of multiple intracellular substrates, within minutes of addition to LPS-nonresponsive cells, followed shortly thereafter by IL-1 alpha secretion. The PTK antagonists genistein and tyrphostin inhibit both tyrosylphosphorylation and cytokine expression. A monoclonal antibody to GPI also blocks IL-1 alpha induction by total parasite extracts. Thus, as in malaria infection, GPI may induce the cytokine excess causing certain pathological states associated with trypanosomiasis. (C) 1994 Academic Press, Inc.
- Publisher
- ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
- Keywords
- VARIANT SURFACE GLYCOPROTEIN; GLYCOSYL-PHOSPHATIDYLINOSITOL; SENSITIVE METHOD; MEMBRANE ANCHOR; T-CELLS; MALARIA; GLYCAN; FORM
- Publisher's Version
- https://doi.org/10.1006/bbrc.1994.2763
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-12-15 12:00:00