ABSTRACT
In this chapter, three specific examples demonstrate how clinical observations of patients with chronic granulomatous disease (CGD) provided the foundation for fundamental insights into the neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Known components of the neutrophil NADPH oxidase include membrane proteins in distinct cellular compartments and soluble proteins in cytoplasm. In unstimulated neutrophils, individual components reside in separate places, leaving the oxidase unassembled and inactive, thereby utilizing spatial segregation as a regulatory feature of the phagocyte oxidase. Essential components of the phagocyte NADPH oxidase that have been identified to date include the membrane heterodimeric protein flavocytochrome b, composed of gp91phox and p22phox, and two cytoplasmic protein complexes of p47phox-p67phox-p40phox and Rac2-RhoGDI. In large part, spatial segregation regulates the activation state of the neutrophil NADPH oxidase. Neutrophil-derived oxidants participate in biological events in addition to those germane to antimicrobial defense.
