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CD95-mediated apoptosis in vivo involves acid sphingomyelinase
S Kirschnek1, F Paris, M Weller
1Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Germany.
The Journal of Biological Chemistry
|June 27, 2000
Summary
Acid sphingomyelinase (ASM) is crucial for CD95-triggered cell death in lymphocytes and liver cells. ASM-deficient mice show resistance to CD95-induced apoptosis, highlighting ASM's vital role in immune regulation and liver health.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Acid sphingomyelinase (ASM) is known to be involved in stress-induced apoptosis.
- The physiological role of ASM in receptor-triggered apoptosis, specifically via the CD95 pathway, remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of Acid sphingomyelinase (ASM) in CD95-mediated apoptosis of peripheral lymphocytes and hepatocytes in vivo.
- To determine the physiological significance of ASM in immune responses and liver homeostasis involving the CD95/CD95 ligand system.
Main Methods:
- Utilized mouse models, including wild-type and ASM knock-out mice.
- Administered intravenous injections of anti-CD4 antibodies or phytohemagglutinin to trigger CD95-mediated apoptosis.
- Assessed apoptosis levels in peripheral blood lymphocytes and hepatocytes ex vivo and in vivo.
Main Results:
- Normal mice exhibited high susceptibility to CD95-triggered apoptosis.
- ASM knock-out mice demonstrated resistance to T cell immunodepletion and developed resistance to autoimmune-like hepatitis.
- ASM-deficient mice, hepatocytes, and splenocytes showed resistance to anti-CD95 treatment ex vivo.
Conclusions:
- Acid sphingomyelinase (ASM) plays a pivotal physiological role in CD95-induced apoptosis of peripheral lymphocytes and hepatocytes.
- ASM is essential for immune regulation, specifically T cell depletion, and maintaining liver homeostasis.
- These findings establish ASM as a key mediator in CD95-driven cell death pathways in vivo.