Phagocytosis-coupled activation of the superoxide-producing phagocyte oxidase, a member of the NADPH oxidase (Nox) family

The phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a crucial role in host defense by neutrophils and macrophages. When cells ingest invading microbes, this enzyme becomes activated to reduce molecular oxygen to superoxide, a precursor of microbicidal oxidants, in the phagosome. The catalytic core of the oxidase is membrane-bound cytochrome b(558), which comprises gp91(phox) and p22(phox). gp91(phox) belongs to the NADPH oxidase (Nox) family, which contains the entire electron-tran sporting apparatus from NADPH to molecular oxygen. In resting neutrophils, cytochrome b(558) is mainly present in the membrane of the specific granule, an intracellular component, and is targeted to the phagosomal membrane during phagocytosis. Activation of gp91(phox) involves the integrated function of cytoplasmic proteins such as p47(phox), p67(phox), p40(phox), and the small guanosine triphosphatase Rac; these proteins translocate to the phagosomal membrane to interact with cytochrome b(558) leading to superoxide production. Here we describe a current molecular model for phagocytosis-coupled activation of the NADPH oxidase.