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 b558, which comprises gp91phox and p22phox. gp91phox belongs to the NADPH oxidase (Nox) family, which contains the entire electron-transporting apparatus from NADPH to molecular oxygen. In resting neutrophils, cytochrome b558 is mainly present in the membrane of the specific granule, an intracellular component, and is targeted to the phagosomal membrane during phagocytosis. Activation of gp91phox involves the integrated function of cytoplasmic proteins such as p47phox, p67phox, p40phox, and the small guanosine triphosphatase Rac; these proteins translocate to the phagosomal membrane to interact with cytochrome b558, leading to superoxide production. Here we describe a current molecular model for phagocytosis-coupled activation of the NADPH oxidase.
Minakami
Reiko
R
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Sumimotoa
Hideki
H
D000818:Animals; D003573:Cytochrome b Group / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000382:microbiology; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism
D003573:Cytochrome b Group; D013481:Superoxides; C036888:cytochrome b558; D019255:NADPH Oxidases; D010100:Oxygen