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Induction of programmed cell death and immunosuppression by exogenous sphingolipids are separate processes
R Olshefski1, B Taylor, A Heitger
1Center for Cancer and Transplantation Biology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010-2970, USA.
European Journal of Biochemistry
|October 1, 1996
Summary
Exogenous ceramides, but not gangliosides, induce programmed cell death (PCD). Gangliosides suppress lymphoproliferation via a distinct mechanism, indicating separate pathways for sphingolipid effects on immune cells.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Gangliosides are immunosuppressive, but their cellular mechanisms are unclear.
- Ceramides, ganglioside metabolites, are implicated as second messengers in programmed cell death (PCD).
Purpose of the Study:
- To investigate the roles of gangliosides and ceramides in inducing PCD.
- To examine their effects on inhibiting in vitro lymphoproliferation.
Main Methods:
- Treatment of cells with exogenous gangliosides (GM3, synthetic variants) and ceramides (C2-ceramide, C6-ceramide).
- Assessment of programmed cell death (PCD) induction.
- Measurement of antigen-induced lymphoproliferation inhibition.
Main Results:
- Short-chain fatty acyl ceramides (C2, C6) induced PCD.
- Gangliosides, including those with PCD-inducing ceramides, did not induce PCD.
- Gangliosides exhibited potent immunosuppressive activity, inhibiting lymphoproliferation at micromolar concentrations.
Conclusions:
- Exogenous sphingolipids inhibit lymphoproliferation and induce PCD through distinct mechanisms.
- Ceramides are direct inducers of PCD, while gangliosides mediate immunosuppression via a separate pathway.