CD95-mediated apoptosis in vivo involves acid sphingomyelinase Journal Article

  


Authors: Kirschnek, S.; Paris, F.; Weller, M.; Grassmé, H.; Ferlinz, K.; Riehle, A.; Fuks, Z.; Kolesnick, R.; Gulbins, E.
Article 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.
Keywords: controlled study; nonhuman; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; apoptosis; fas antigen; animalia; liver; enzyme analysis; liver cell; lymphocyte; lymphocyte depletion; knockout mouse; immunopathogenesis; sphingomyelin phosphodiesterase; autoimmune hepatitis; antigens, cd95; priority journal; article
Journal Title: Journal of Biological Chemistry
Volume: 275
Issue: 35
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2000-09-01
Start Page: 27316
End Page: 27323
Language: English
DOI: 10.1074/jbc.M002957200
PUBMED: 10867001
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0034282716&partnerID=40&md5=59ea7de5546c1f7f60232a999369f74b
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Zvi Fuks
    428 Fuks
  2. Francois Paris
    19 Paris
  3. Richard N Kolesnick
    300 Kolesnick
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