Disruption of fas receptor signaling by nitric oxide in eosinophils.
- Hebestreit H Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, CH-7270 Davos, Switzerland.
- Dibbert B
- Balatti I
- Braun D
- Schapowal A
- Blaser K
- Simon HU
- 1998-03-21
Published in:
- The Journal of experimental medicine. - 1998
Apoptosis
Cell Survival
Coculture Techniques
Eosinophils
Fas Ligand Protein
Flow Cytometry
Gene Expression Regulation, Neoplastic
Histocytochemistry
Humans
Immunoblotting
Membrane Glycoproteins
Nasal Polyps
Nitric Oxide
Nitric Oxide Synthase
RNA
Second Messenger Systems
Signal Transduction
Tumor Cells, Cultured
English
It has been suggested that Fas ligand-Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor-mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor-mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme-like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1084/jem.187.3.415
- PMID 9449721
- Persistent URL
- https://sonar.ch/global/documents/22850
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