NADPH oxidase NOX2 mediates rapid cellular oxidation following ATP stimulation of endotoxin-primed macrophages

Samantha F Moore, Amanda B MacKenzie

Research output: Contribution to journalArticle (Academic Journal)peer-review

63 Citations (Scopus)

Abstract

The phagocytic NADPH oxidase (NOX2) plays a fundamental role in host defense and innate immunity. Here we demonstrate that external ATP triggers rapid cellular oxidation inhibited by diphenyleneiodonium in endotoxin-primed J774 macrophages and primary murine bone marrow-derived macrophages. To identify the source of reactive oxygen species (ROS), we compared responses between wild-type and NOX2-deficient macrophages. ATP-mediated ROS production was strongly attenuated in NOX2-deficient macrophages where responses were comparable to inhibition with diphenyleneiodonium. Notably, spatial differences in superoxide anion formation were observed where ROS formation was partially antagonized by extracellular superoxide dismutase in primary bone marrow-derived macrophages but unaffected in J774 macrophages. Loss of NOX2 was not observed to affect ATP-induced cell death. However, ATP-evoked cell death was found to be partially dependent on caspase-1 and cathepsin B activation. In conclusion, NOX2 plays a fundamental role in conferring macrophages with the ability to respond to extracellular ATP stimulation with robust changes in cellular oxidation.
Original languageEnglish
Pages (from-to)3302-8
Number of pages7
JournalJournal of Immunology
Volume183
Issue number5
DOIs
Publication statusPublished - 1 Sep 2009

Keywords

  • Endotoxins
  • Macrophages
  • Animals
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Oxidation-Reduction
  • Bone Marrow Cells
  • Extracellular Fluid
  • Cells, Cultured
  • NADPH Oxidase
  • Isoenzymes
  • Mice, Inbred C57BL
  • Lipopolysaccharides
  • Adenosine Triphosphate
  • Phagocytosis
  • Cell Line

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