Open AccessInduction of Programmed Cell Death and Immunosuppression by Exogenous Sphingolipids are Separate Processes
Author(s) -
Olshefski Randal,
Taylor Barbara,
Heitger Andreas,
Hasegawa Akira,
Ladisch Stephan
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.0047t.x
Subject(s) - ceramide , sphingolipid , sphingosine , programmed cell death , lipid signaling , second messenger system , sphingomyelin , biology , biochemistry , in vitro , apoptosis , microbiology and biotechnology , chemistry , enzyme , cholesterol , receptor
Gangliosides are highly immunosuppressive molecules but the mechanism(s) by which they act upon cells remains to be fully defined. Several metabolic products of exogenous gangliosides, including ceramide, have recently been suggested as second messengers in programmed cell death (PCD). Therefore, we have probed the role of gangliosides and ceramides in the induction of PCD and in the inhibition of in vitro lymphoproliferation. PCD was caused only by exogenous ceramides with short fatty acyl groups‐ d18:1‐C2:O (C 2 ‐ceramide, where d18:1 is sphingosine and C2:O is an acetyl group) and d18:1–C6:0 (C 6 ‐ceramide, where C6:O is a hexanoyl group). None of the gangliosides studied induced PCD, including naturally occurring G M3 synthetic d18:1‐C18:0 G M3 (C 18 ‐Cer G M3 , where C18:0 is a stearoyl group), or even d18:1‐C2:0 G M3 (C 2 ‐Cer G M3 ), which itself contains a PCD‐causing ceramide. However, these gangliosides were highly immunosuppressive, inhibiting antigen‐induced lymphoproliferation at micromolar concentrations. We conclude that exogenous sphingolipids cause inhibition of lymphoproliferation and PCD by two separate and distinct mechanisms of action.