β-Glycosphingolipids-mediated lipid raft alteration is associated with redistribution of NKT cells and increased intrahepatic CD8+ T lymphocyte trapping

• Published in: Journal of lipid research Vol. 49; no. 9; pp. 1884 - 1893
• Main Authors: Lalazar, Gadi, Ben Ya'acov, Ami, Eliakim-Raz, Noa, Livovsky, Dan M., Pappo, Orit, Preston, Sarah, Zolotarov, Lidya, Ilan, Yaron
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2008; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes - immunology; Colitis - chemically induced; Colitis - drug therapy; Colitis - immunology; Colitis - pathology; Cytokines - blood; Glycosphingolipids - physiology; Glycosphingolipids - therapeutic use; Killer Cells, Natural - immunology; lipid rafts; Liver - cytology; liver tolerance; Male; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Mice; Mice, Inbred C57BL; natural killer T cell; Spleen - cytology; T-Lymphocytes - physiology; Trinitrobenzenesulfonic Acid; lipid rafts; natural killer T cell; liver tolerance
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M800113-JLR200

The aim of this study was to determine the effect of β-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 β-lactosylceramide (LC), β-glucosylceramide (GC), β-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 β-glycosphingolipids resulted in an increased intrahepatic/peripheral NKT ratio, increased intrahepatic CD8+ lymphocyte trapping, decreased serum interferon-γ (IFN-γ) levels and decreased serum IFN-γ/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 β-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 β-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.