Regulatory roles of cell surface sialylation in sphingolipid-induced cell death in human B cell lymphoma.
Sphingolipid metabolites are important regulators of cell growth and death. In the present study, we examined the function of cell surface sialic acid in exogenous sphingosine-1-phosphate (S-1-P) or sphingosine-induced cell death. HBL-2 human diffuse large B cell lymphoma cells were incubated with or without Vibrio Cholerae neuraminidase followed by S-1-P or sphingosine. Flow cytometric analysis using Limax flavus agglutinin, a sialic acid-specific lectin, showed that sialylated glycoconjugates are present on the surface of HBL-2 cells and that they were removed by neuraminidase. In addition, the pretreatment with neuraminidase enhanced S-1-P- and sphingosine-induced cell death, an effect that was not dependent on caspase activation. Furthermore, the cell death induced by S-1-P and sphingosine was morphologically distinct from apoptosis. We further examined S-1-P-induced cell death in two clones of HBL-8 Burkitt lymphoma cells with different amounts of cell surface sialic acid. Clone 3G3, which is hypersialylated, was less sensitive to S-1-P than the 3D2 clone, which is hyposialylated, suggesting that the extent of surface sialylation influences the sensitivity to S-1-P. In conclusion, S-1-P and sphingosine induce cell death, and the sensitivity of human B lymphoma cells to these agents appears to depend on the amount of sialic acid on their cell surfaces.
Suzuki
Osamu
O
Fukushima Medical University, School of Medicine, Department of Pathology, Fukushima 960-1295, Japan. osuzuki@fmu.ac.jp
Nozawa
Yoshihiro
Y
Abe
Masafumi
M
D000373:Agglutinins / Q000737:chemistry; D000818:Animals; D019921:Biotinylation; D016923:Cell Death; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D008954:Models, Biological; D009439:Neuraminidase / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry*; D013107:Sphingolipids / Q000737:chemistry*; D014734:Vibrio cholerae / Q000378:metabolism
D000373:Agglutinins; D012794:Sialic Acids; D013107:Sphingolipids; D009439:Neuraminidase