Immunomodulatory properties of Ascaris suum glycosphingolipids -: phosphorylcholine and non-phosphorylcholine-dependent effects

被引:35
作者
Deehan, MR
Goodridge, HS
Blair, D
Lochnit, G
Dennis, RD
Geyer, R
Harnett, MM
Harnett, W [1 ]
机构
[1] Univ Strathclyde, Dept Immunol, Strathclyde Inst Biomed Sci, Glasgow G4 0NR, Lanark, Scotland
[2] Univ Glasgow, Dept Immunol, Glasgow, Lanark, Scotland
[3] Univ Giessen, Giessen, Germany
关键词
apoptosis; Ascaris; glycosphingolipid; immunomodulation; phosphorylcholine;
D O I
10.1046/j.1365-3024.2002.00489.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:463 / 469
页数:7
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