Intersecting Stories of the Phagocyte NADPH Oxidase and Chronic Granulomatous Disease

  • William M. Nauseef
  • Robert A. ClarkEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1982)


Neutrophils serve as the circulating cells that respond early and figure prominently in human host defense to infection and in inflammation in other settings. Optimal oxidant-dependent antimicrobial activity by neutrophils relies on the ability of stimulated phagocytes to utilize a multicomponent NADPH oxidase to generate oxidants. The frequent, severe, and often fatal infections experienced by individuals with chronic granulomatous disease (CGD), an inherited disorder in which one of the NADPH oxidase components is absent or dysfunctional, underscore the link between a functional phagocyte NADPH oxidase and robust host protection against microbial infection.

The history of the discovery and characterization of the normal neutrophil NADPH oxidase and the saga of recognizing CGD and its underlying causes together illustrate how the observations of astute clinicians and imaginative basic scientists synergize to forge new understanding of both basic cell biology and pathogenesis of human disease.

In this chapter, we review the events in the stepwise evolution of our understanding of the phagocyte NADPH oxidase, both in the context of normal human neutrophil function and in the setting of CGD. The phagocyte oxidase complex employs a heterodimeric transmembrane protein composed of gp91phox and p22phox to relay electrons from NADPH to molecular oxygen, while other cofactors contribute to localization and regulation of the activity of the assembled oxidase. The b-type cytochrome gp91phox, also known as NOX2, serves as the catalytic component of this multicomponent enzyme complex. Although many of the features of the composition and regulation of the phagocyte oxidase may apply as well to NOX2 expressed in non-phagocytes and to other members of the NOX protein family, exceptions exist and pose special challenges to investigators exploring the biology of NADPH oxidases.

Key words

Phagocyte NADPH oxidase NOX2 gp91phox p22phox Cytochrome b558 p47phox p67phox p40phox Chronic granulomatous disease (CGD) 



The authors have been supported by grants from the National Institutes of Health [R01- AI132335 (WMN); R01-AI16546 (WMN); UL1-TR002645 (RAC); P30-AG044271 (RAC); R01-AI020866 (RAC)] and the Veterans Health Administration [I01 BX000513 (WMN); I01-BX000117 (RAC); I01-BX003157 (RAC)].


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Inflammation Program, Department of Medicine, Roy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa CityUSA
  2. 2.Institute for Integration of Medicine and Science and Department of MedicineUniversity of Texas Health Science Center, and South Texas Veterans Healthcare SystemSan AntonioUSA

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