Induction of gp91-phox, a Component of the Phagocyte NADPH Oxidase, in Microglial Cells during Central Nervous System Inflammation

Abstract

Gp91-phox is an integral component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex that generates reactive oxygen species (ROS) in activated circulating phagocytes. The authors previously demonstrated that gp91-phox knockout (KO) mice show significant protection from neuronal injury after cerebral ischemia--reperfusion injury, suggesting a pivotal role for this enzyme. Moreover, results from chimeric mice suggested that elimination of gp91-phox from both circulating phagocytes and a putative central nervous system (CNS) source were required to confer neuroprotection. In the current study, the authors demonstrated gp91-phox-specific immunostaining of perivascular cells in the CNS of control rats. However, after transient cerebral ischemia, gp91-phox-positive phagocytes were observed within the core ischemic region and activated microglial cells were positive in the penumbra. Such activated microglial cells were also gp91-phox-positive in the CNS of a chimpanzee with mild meningitis. Finally, in humans, both normal adult CNS tissues and isolated fetal microglial cells expressed gp91-phox mRNA. These microglia also expressed mRNA for the five other known components that comprise the NADPH oxidase complex. These data strongly suggest that microglial cells may contain a functionally active NADPH oxidase capable of generating ROS during CNS inflammation.

Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes

“…In contrast, astrocytes and preOLs did not express detectable NADPH oxidase. These results do not, however, exclude the possibility that the oxidase can be transcriptionally up-regulated in these cells under certain pathophysiological conditions (37). In fact, exposure to zinc results in up-regulation of NADPH oxidase in cultured cortical neurons and astrocytes, and this up-regulation may contribute to zincinduced neuronal death (38).…”

NADPH Oxidase Mediates Lipopolysaccharide-induced Neurotoxicity and Proinflammatory Gene Expression in Activated Microglia

“…Microglia are considered the resident immune cells in the brain (44,45), where NADPH oxidase activation is known to be associated with neuroinflammation (46). Under normal conditions, microglia serve a crucial role in immune surveillance.…”

MUNC13-4 Protein Regulates the Oxidative Response and Is Essential for Phagosomal Maturation and Bacterial Killing in Neutrophils

“…S1. The generation and characterization of the anti-gp91 phox monoclonal antibody 18C7 were described previously (45). The rabbit polyclonal antibody raised against MUNC13-4 was described previously (27).…”