Publication: Involvement of a functional NADPH oxidase in neutrophils and macrophages during programmed cell clearance: Implications for chronic granulomatous disease
Issued Date
2009-09-01
Resource Type
ISSN
15221563
03636143
03636143
Other identifier(s)
2-s2.0-70349244722
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Physiology - Cell Physiology. Vol.297, No.3 (2009)
Suggested Citation
Duangmanee Sanmun, Erika Witasp, Siriporn Jitkaew, Yulia Y. Tyurina, Valerian E. Kagan, Anders Åhlin, Jan Palmblad, Bengt Fadeel Involvement of a functional NADPH oxidase in neutrophils and macrophages during programmed cell clearance: Implications for chronic granulomatous disease. American Journal of Physiology - Cell Physiology. Vol.297, No.3 (2009). doi:10.1152/ajpcell.00651.2008 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27156
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Involvement of a functional NADPH oxidase in neutrophils and macrophages during programmed cell clearance: Implications for chronic granulomatous disease
Abstract
Resolution of inflammation requires clearance of activated neutrophils by macrophages in a manner that prevents injury to adjacent tissues. Surface changes, including phosphatidylserine (PS) exposure, may target neutrophils for phagocytosis. In this study, we show that externalization of PS is defective in phorbol myristate acetate (PMA)-activated neutrophils obtained from chronic granulomatous disease (CGD) patients with mutations in components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Moreover, activated neutrophils from CGD patients failed to undergo clearance upon cocultivation with macrophages from normal donors. In line with these results, treatment of donor neutrophils with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase, blocked PMA-induced PS oxidation and externalization and prevented their engulfment by macrophages. Furthermore, primary macrophages from CGD patients or human gp91phox-deficient PLB-985 cells differentiated into macrophage-like cells were defective for engulfment of apoptotic target cells. Pretreatment of normal macrophages with DPI also suppressed the subsequent ingestion of PS-positive target cells. Together, these data demonstrate that NADPH oxidase plays an important role in the process of macrophage disposal of target cells (programmed cell clearance). Thus we speculate that the lack of a functional NADPH oxidase results in impaired neutrophil clearance and the exaggerated inflammation that is characteristic for CGD. Copyright © 2009 the American Physiological Society.