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Originally published online as doi:10.1189/jlb.0908525 on January 13, 2009

Published online before print January 13, 2009
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(Journal of Leukocyte Biology. 2009;85:497-507.)
© 2009 by Society for Leukocyte Biology

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§, Bob Asselbergh§, Peter Vandenabeele{dagger},{ddagger} and Jean Willems*,1

* 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
§ Microscopy Core Facility, Department for Molecular Biomedical Research, VIB, Ghent University, Ghent, Belgium

1 Correspondence: IRC, Dept. of Medicine, Laboratory of Biochemistry, K.U.L. Campus Kortrijk, E. Sabbelaan 53, 8500 Kortrijk, Belgium. E-mail: jean.willems{at}kuleuven-kortrijk.be

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