CD95-mediated apoptosis in vivo involves acid sphingomyelinase.
Acid sphingomyelinase (ASM) is reported to have an essential function in stress-induced apoptosis although the physiological function of ASM in receptor-triggered apoptosis is unknown. Here, we delineate a pivotal role for ASM in CD95-triggered apoptosis of peripheral lymphocytes or hepatocytes in vivo. We employed intravenous injection of anti-CD4 antibodies or phytohemagglutinin that was previously shown to result in apoptosis of peripheral blood lymphocytes or hepatocytes via the endogenous CD95/CD95 ligand system. Our results demonstrate a high susceptibility in normal mice whereas ASM knock-out mice fail to immunodeplete T cells or develop autoimmune-like hepatitis. Likewise, ASM-deficient mice or hepatocytes and splenocytes ex vivo manifest resistance to anti-CD95 treatment. These results provide in vivo evidence for an important physiological function of ASM in CD95-induced apoptosis.
Kirschnek
S
S
Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Germany.
Paris
F
F
Weller
M
M
Grassme
H
H
Ferlinz
K
K
Riehle
A
A
Fuks
Z
Z
Kolesnick
R
R
Gulbins
E
E
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D019014:fas Receptor / Q000276:immunology*
D019014:fas Receptor; D013108:Sphingomyelin Phosphodiesterase