Sp. Green et al., Induction of gp91-phox, a component of the phagocyte NADPH oxidase, in microglial cells during central nervous system inflammation, J CEREBR B, 21(4), 2001, pp. 374-384
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.