Immunomodulatory properties of Ascaris suum glycosphingolipids - phosphorylcholine and non-phosphorylcholine-dependent effects.
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-gamma 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.
Deehan
Maureen R
MR
Department of Immunology, University of Glasgow, UK. w.harnett@strath.ac.uk
Goodridge
Helen S
HS
Blair
Derek
D
Lochnit
Gunter
G
Dennis
Roger D
RD
Geyer
Rudolf
R
Harnett
Margaret M
MM
Harnett
William
W
D000818:Animals; D017209:Apoptosis; D017165:Ascaris suum / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006028:Glycosphingolipids / Q000737:chemistry / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010767:Phosphorylcholine / Q000276:immunology*
D016207:Cytokines; D006028:Glycosphingolipids; D008070:Lipopolysaccharides; D010767:Phosphorylcholine; D020928:Mitogen-Activated Protein Kinases