1. Immunomodulatory properties of Ascaris suum glycosphingolipids - phosphorylcholine and non-phosphorylcholine-dependent effects
- Author
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William Harnett, Roger D. Dennis, Margaret M. Harnett, Helen S. Goodridge, Rudolf Geyer, Derek Blair, Maureen R. Deehan, and Günter Lochnit
- Subjects
Lipopolysaccharides ,Phosphorylcholine ,medicine.medical_treatment ,Immunology ,Apoptosis ,Biology ,Lymphocyte Activation ,Glycosphingolipids ,Mice ,chemistry.chemical_compound ,medicine ,Animals ,Ascaris suum ,B cell ,B-Lymphocytes ,Mice, Inbred BALB C ,Glycosphingolipid ,Cell cycle ,biology.organism_classification ,medicine.anatomical_structure ,Cytokine ,chemistry ,Macrophages, Peritoneal ,Cytokines ,lipids (amino acids, peptides, and proteins) ,Parasitology ,Mitogen-Activated Protein Kinases ,Signal transduction - Abstract
SUMMARY Immunomodulatory properties of phosphorylcholine (PC)-containing glycosphingolipids from Ascaris suum were investigated utilizing immune cells from BALB/c mice. Proliferation of splenic B cells induced either via F(ab′)2 fragments of anti-murine Ig (anti-Ig) or LPS was significantly reduced when the glycosphingolipids were present in the culture medium. However whereas the LPS-mediated effect was dependent on the PC moiety of the glycosphingolipids, the result generated when using anti-Ig was not. Analysis of cell cycle status and mitochondrial potential indicated that the combination of the glycosphingolipids and anti-Ig reduced B cell proliferation, at least in part, by inducing apoptosis. Consistent with the observed suppression of B cell activation/cell cycle progression, investigation of the effect of glycosphingolipid pre-exposure on mitogenic B cell signal transduction pathways activated by anti-Ig, revealed a PC-independent inhibitory effect on dual (thr/tyr) phosphorylation and activation of ErkMAPKinase. The glycosphingolipids were also investigated for their inhibitory effect on LPS/IFN-γ induced Th1/pro-inflammatory cytokine production by peritoneal macrophages. It was found that IL-12 p40 production was inhibited and in an apparently PC-dependent manner. Overall these data indicate that PC-containing glycosphingolipids of A. suum appear to have at least two immunomodulatory constituents – PC and an as yet unknown component.
- Published
- 2002
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