Phagocytosis-Coupled Activation of the Superoxide-Producing Phagocyte Oxidase, a Member of the NADPH Oxidase (Nox) Family
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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 gp91 phox and p22 phox . gp91 phox 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 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 b558, leading to superoxide production. Here we describe a current molecular model for phagocytosis-coupled activation of the NADPH oxidase.
Key wordsNADPH oxidase Nox Neutrophil Phagocytosis Phagosome Superoxide
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- 9.Garcia-Garcia E, Rosales C. Signal transduction during Fc receptor-mediated phagocytosis. J Leukoc Biol. 2002;72:1092–1108.Google Scholar
- 15.Castellano F, Montcourrier P, Chavrier P. Membrane recruitment of Rac1 triggers phagocytosis. J Cell Sci. 2000;113:2955–2961.Google Scholar
- 23.Ago T, Nunoi H, Ito T, Sumimoto H. Mechanism for phosphorylationinduced activation of the phagocyte NADPH oxidase protein p47phox: triple replacement of serines 303, 304, and 328 with aspartates disrupts the SH3 domain-mediated intramolecular interaction in p47phox, thereby activating the oxidase. J Biol Chem. 1999;274:33644–33653.CrossRefGoogle Scholar
- 29.El Benna J, Faust LP, Babior BM. The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation: phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. J Biol Chem. 1994;269:23431–23436.Google Scholar
- 42.Gorzalczany Y, Alloul N, Sigal N, Weinbaum C, Pick E. A prenylated p67phox-Rac1 chimera elicits NADPH-dependent superoxide production by phagocyte membranes in the absence of an activator and of p47phox: conversion of a pagan NADPH oxidase to monotheism. J Biol Chem. 2002;277:18605–18610.CrossRefGoogle Scholar