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Oxidant‐mediated phosphatidylserine exposure and macrophage uptake of activated neutrophils: possible impairment in chronic granulomatous disease
Author(s) -
Hampton Mark B.,
Vissers Margret C. M.,
Keenan Jacqueline I.,
Winterbourn Christine C.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.5.775
Subject(s) - chronic granulomatous disease , nadph oxidase , phagocytosis , phosphatidylserine , inflammation , elastase , biology , immunology , respiratory burst , phagocyte , macrophage , myeloperoxidase , staphylococcus aureus , chemotaxis , monocyte , granulocyte , neutrophile , p22phox , receptor , in vitro , microbiology and biotechnology , reactive oxygen species , enzyme , biochemistry , bacteria , phospholipid , genetics , membrane
The removal of neutrophils from inflammatory sites is essential for the resolution of inflammation. Surface changes, including phosphatidylserine exposure, label neutrophils for phagocytosis by macrophages. Here, we demonstrate that externalization of phosphatidylserine and uptake by monocyte‐derived macrophages occurred in human neutrophils ingesting Staphylococcus aureus . Both processes were dependent on oxidant production from the neutrophil NADPH oxidase. There was no requirement for myeloperoxidase, and H 2 O 2 was identified as the most likely trigger for PS exposure. We hypothesize that clearance of stimulated neutrophils would be delayed in chronic granulomatous disease (CGD) neutrophils, which lack a functional NADPH oxidase. To explore this possibility, heat‐killed S. aureus were injected into the peritoneum of CGD and normal mice. Elevated neutrophil numbers were observed in the inflammatory exudate of the CGD animals, consistent with impaired recognition and clearance.