Current address: Lead Discovery Pharmacology, Organon Laboratories Ltd, Newhouse, ML1 5SH, UK.
Immunomodulatory properties of Ascaris suum glycosphingolipids – phosphorylcholine and non-phosphorylcholine-dependent effects
Article first published online: 21 MAR 2003
Volume 24, Issue 9-10, pages 463–469, September 2002
How to Cite
Deehan, M. R., Goodridge, H. S., Blair, D., Lochnit, G., Dennis, R. D., Geyer, R., Harnett, M. M. and Harnett, W. (2002), Immunomodulatory properties of Ascaris suum glycosphingolipids – phosphorylcholine and non-phosphorylcholine-dependent effects. Parasite Immunology, 24: 463–469. doi: 10.1046/j.1365-3024.2002.00489.x
- Issue published online: 21 MAR 2003
- Article first published online: 21 MAR 2003
- Received: 10 July 2002; Accepted for publication: 30 October 2002
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.