Accuri C6 Flow Cytometer System
A more recent version of this article appeared on March 1, 2009

Published online before print January 13, 2009
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow Supplemental Video
Right arrow All Versions of this Article:
jlb.0908525v1
85/3/497    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Remijsen, Q.
Right arrow Articles by Willems, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Remijsen, Q.
Right arrow Articles by Willems, J.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0908525

Received for publication September 5, 2008.
Revised October 15, 2008.
Accepted for publication November 13, 2008.

Article

Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt

Quinten Remijsen *, Tom Vanden Berghe {dagger}{ddagger}, Eef Parthoens {sect}, Bob Asselbergh {sect}, Peter Vandenabeele {dagger}{ddagger}, and Jean Willems *@

*IRC, Department of Medicine Laboratory of Biochemistry, K.U. Leuven Campus Kortrijk, Kortrijk, Belgium; {dagger}Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; and {ddagger}Molecular Signaling and Cell Death Unit, Department for Molecular Biology, and {sect}Microscopy Core Facility, Department for Molecular Biomedical Research, VIB, Ghent University, Ghent, Belgium
*IRC, Department of Medicine Laboratory of Biochemistry, K.U. Leuven Campus Kortrijk, Kortrijk, Belgium; {dagger}Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; and Dagger;Molecular Signaling and Cell Death Unit, Department for Molecular Biology, and {sect}Microscopy Core Facility, Department for Molecular Biomedical Research, VIB, Ghent University, Ghent, Belgium

@ To whom correspondence should be addressed. E-mail: jean.willems{at}kuleuven-kortrijk.be.


arrow
Abstract

Neutrophil cell death plays a crucial role in neutrophil homeostasis and the resolution of inflammation. The superoxide-producing NADPH oxidase is involved in pathogen degradation and subsequent activation of cell death programs. Neutrophils from patients with chronic granulomatous disease, who have a deficient NADPH oxidase activity, have been demonstrated previously to have a prolonged lifespan, suggesting that a basal NADPH oxidase activity also regulates spontaneous neutrophil turnover. The NADPH oxidase inhibitor parabutoporin (PP) does delay spontaneous apoptosis, but this effect is completely independent of NADPH oxidase inhibition. Instead, the prosurvival effect of PP depends on activation of protein kinase B/Akt via lipid raft signaling. Disruption of lipid rafts abrogates the prosurvival effect without interfering with NADPH oxidase activity. Furthermore, we cannot detect a different rate of spontaneous apoptosis between normal and NADPH oxidase-deficient neutrophils, arguing against a role of NADPH oxidase in spontaneous neutrophil apoptosis.

Key Words: granulocyte • chronic granulomatous disease • superoxide • scorpion