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. |