Abstract
The aim of this study was to determine the effect of beta-glycosphingolipids on intra-hepatic natural killer T (NKT) lymphocyte regulatory function and on lymphocyte trapping via alteration of cell membrane lipid rafts. Immune-mediated colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Mice were treated with beta-lactosylceramide (LC), beta-glucosylceramide (GC), beta-galactosylceramide, ceramide, or a combination of both GC and LC (IGL), or solvent alone. Lipid rafts were investigated by fluorescence-activated cell sorting analysis of ganglioside-GM1 and fluorescence microscopy of structure. Administration of beta-glycosphingolipids resulted in an increased intrahepatic/peripheral NKT ratio, increased intrahepatic CD8+ lymphocyte trapping, decreased serum interferon-gamma (IFN-gamma) levels and decreased serum IFN-gamma/interleukin-10 ratio. Administration of GC, LC, or IGL significantly altered the levels of GM1, a key marker of lipid rafts, on NKT regulatory lymphocytes. The immune modulatory effect of beta-glycosphingolipids was associated with increased survival and significant alleviation of colitis as determined by improvement in both the macroscopic and microscopic scores. In conclusion, administration of beta-glycosphingolipids increased NKT regulatory lymphocyte redistribution and intrahepatic CD8(+) T lymphocyte trapping, resulting in alleviation of immune-mediated colitis. The effects of these naturally occurring compounds were associated with modification of the T lymphocyte lipid raft structure, which is a site for immune modulation.
Highlights
Lymphocyte regulatory function and on lymphocyte trapping via alteration of cell membrane lipid rafts
These results suggest that GC administration can overcome the suppressive effect of LC on Natural killer T (NKT) cells in this setting
No significant effect on the peripheral NKT cell number was noted by fluorescence-activated cell sorting (FACS) analysis of intrasplenic NKT lymphocytes (Fig. 1B)
Summary
Lymphocyte regulatory function and on lymphocyte trapping via alteration of cell membrane lipid rafts. Administration of b-glycosphingolipids increased NKT regulatory lymphocyte redistribution and intrahepatic CD81 T lymphocyte trapping, resulting in alleviation of immune-mediated colitis. The effects of these naturally occurring compounds were associated with modification of the T lymphocyte lipid raft structure, which is a site for immune modulation.—Lalazar, G., A. B-Glycosphingolipids-mediated lipid raft alteration is associated with redistribution of NKT cells and increased intrahepatic CD81 T lymphocyte trapping. Natural killer T (NKT) cells, a subset of regulatory lymphocytes, are considered players in the innate immune system [4] Via their T cell receptor (TCR), these cells recognize glycosphingolipids anchored by a ceramide tail to CD1d, which is a major histocompatibility complex (MHC), class I-like molecule [5].
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