Conus, Sébastien; Perozzo, Remo; Reinheckel, Thomas; Peters, Christoph; Scapozza, Leonardo; Yousefi, Shida; Simon, Hans-Uwe (2008). Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. Journal of experimental medicine, 205(3), pp. 685-698. New York, N.Y.: Rockefeller University Press 10.1084/jem.20072152
Full text not available from this repository. (Request a copy)In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species-dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Conus, Sébastien, Simon, Hans-Uwe |
ISSN: |
0022-1007 |
ISBN: |
18299403 |
Publisher: |
Rockefeller University Press |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:54 |
Last Modified: |
05 Dec 2022 14:16 |
Publisher DOI: |
10.1084/jem.20072152 |
PubMed ID: |
18299403 |
Web of Science ID: |
000254173100017 |
URI: |
https://boris.unibe.ch/id/eprint/23057 (FactScience: 38753) |
Actions (login required)
 |
Edit item |