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Publication : CD95-mediated apoptosis in vivo involves acid sphingomyelinase.

First Author  Kirschnek S Year  2000
Journal  J Biol Chem Volume  275
Issue  35 Pages  27316-23
PubMed ID  10867001 Mgi Jnum  J:115330
Mgi Id  MGI:3691394 Doi  10.1074/jbc.M002957200
Citation  Kirschnek S, et al. (2000) CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J Biol Chem 275(35):27316-23
abstractText  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.
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