Induction of gp91-phox, a component of the phagocyte NADPH oxidase, in microglial cells during central nervous system inflammation

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 demonstrat ed that gp91-phox knockout (KO) mice show significant protection from neuro nal 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 ce ntral nervous system (CNS) source were required to confer neuroprotection. In the current study, the authors demonstrated gp91-phox-specific immunosta ining of perivascular cells in the CNS of control rats. However, after tran sient cerebral ischemia, gp91-phox-positive phagocytes were observed within the core ischemic region and activated microglial cells were positive in t he penumbra. Such activated microglial cells were also gp91-phox-positive i n the CNS of a chimpanzee with mild meningitis. Finally, in humans, both no rmal adult CNS tissues and isolated fetal microglial cells expressed gp91-p hox mRNA. These microglia also expressed mRNA for the five other known comp onents that comprise the NADPH oxidase complex. These data strongly suggest that microglial cells may contain a functionally active NADPH oxidase capa ble of generating ROS during CNS inflammation.