The NADPH oxidase of neutrophils and other cells

Neutrophils and other “professional” phagocytes (including monocytes, macrophages and eosinophils) have an important role in the response of the immune system to microbial infections. They are attracted to infection sites by chemoattractants secreted by the excited cells of the immune system, by tissue cells such as endothelial cells and fibroblasts, and by peptides derived from disrupted bacteria. Complement activation generates fragment C5a which is an important attractant for phagocytes. There are receptors on the neutrophil plasma membrane for these attractants and activation of the receptors initiates a complex series of events which prepare the neutrophil for its cytocidal role [1]. The primed neutrophils move to the target opsonised microbes, phagocytose, kill and digest them. The killing process involves the release of an array of granule proteins into the developing phagosome as the neutrophil degranulates and the activation of a plasma membrane NADPH oxidase which forms superoxide radicals and directs these into the phagocytic vacuole. Superoxide is unstable and reactive and is the progenitor of a family of reactive oxygen species (ROS). These are themselves microbicidal and can also act in concert with the granule-derived proteins to increase their cytotoxicity. The importance of the production of superoxide by NADPH oxidase is clearly demonstrated in the rare genetic condition of chronic granulomatous disease (CGD). The patients with this defect have neutrophils lacking in NADPH oxidase which are unable to form superoxide, with the consequence that the patients suffer chronic infections because they are unable to mount an effective attack on the pathogen.