Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation

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

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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)