Oxidant-mediated phosphatidylserine exposure and macrophage uptake of activated neutrophils: possible impairment in chronic granulomatous disease.
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.
Hampton
Mark B
MB
Department of Pathology, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand. mark.hampton@chmeds.ac.nz
Vissers
Margret C M
MC
Keenan
Jacqueline I
JI
Winterbourn
Christine C
CC
D000293:Adolescent; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004705:Endocytosis; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D016877:Oxidants / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D013211:Staphylococcus aureus
D016877:Oxidants; D010718:Phosphatidylserines; D009195:Peroxidase