The Journal of Experimental Medicine
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online February 25, 2008
doi:10.1084/jem.20072152
The Journal of Experimental Medicine, Vol. 205, No. 3, 685-698
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Conus et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Conus, S.
Right arrow Articles by Simon, H.-U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Conus, S.
Right arrow Articles by Simon, H.-U.
Related Collections
Right arrowRelated In this Issue article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

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

Sébastien Conus1, Remo Perozzo2, Thomas Reinheckel3, Christoph Peters3, Leonardo Scapozza2, Shida Yousefi1, and Hans-Uwe Simon1

1 Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
2 Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, 1211 Geneva 4, Switzerland
3 Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, Germany

CORRESPONDENCE Hans-Uwe Simon: hus{at}pki.unibe.ch

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.

Abbreviations used: CA, CA-074-ME; CGD, chronic granulomatous disease; DPI, diphenyleneiodonium; MPO, myeloperoxidase; NADPH, nicotinamide adenine dinucleotide phosphate; PepA, pepstatin A; PI, propidium iodide; PS, phosphatidylserine; ROS, reactive oxygen species; SCLC, small cell lung carcinoma.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related In this Issue article

Granules live and let die
Hema Bashyam
J. Exp. Med. 2008 205: 505. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS