title: CD95-mediated apoptosis in vivo involves acid sphingomyelinase.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kirschnek
authors.forename: F
authors.initials: F
authors.lastname: Paris
authors.forename: M
authors.initials: M
authors.lastname: Weller
authors.forename: H
authors.initials: H
authors.lastname: Grassme
authors.forename: K
authors.initials: K
authors.lastname: Ferlinz
authors.forename: A
authors.initials: A
authors.lastname: Riehle
authors.forename: Z
authors.initials: Z
authors.lastname: Fuks
authors.forename: R
authors.initials: R
authors.lastname: Kolesnick
authors.forename: E
authors.initials: E
authors.lastname: Gulbins
mesh_terms: 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*
chemical_list: D019014:fas Receptor; D013108:Sphingomyelin Phosphodiesterase