Abstract

Phagocytes such as neutrophils play a vital role in host defense against microbial pathogens. The anti-microbial function of neutrophils is based on the production of superoxide anion (O2 -), which generates other microbicidal reactive oxygen species (ROS) and release of antimicrobial peptides and proteins. The enzyme responsible for O2 - production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans- membrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate agents. This process is dependent on the phosphorylation of the cytosolic protein p47phox. p47phox is a 390 amino acids protein with several functional domains: one phox homology (PX) domain, two src homology 3 (SH3) domains, an auto-inhibitory region (AIR), a proline rich domain (PRR) and has several phosphorylated sites located between Ser303 and Ser379. In this review, we will describe the structure of p47phox, its phosphorylation and discuss how these events regulate NADPH oxidase activation.

Highlights

  • Phagocytes such as polymorphonuclear neutrophils, eosinophils, monocytes and macrophages constitute one of the most powerful means of host defense against bacteria and fungi (Segal, 2005; Nathan, 2006)

  • The phagocyte NADPH oxidase and reactive oxygen species (ROS) production play a key role in host defense against microbial pathogens as illustrated by a human genetic disorder called chronic granulomatous disease (CGD), which is associated with life-threatening bacterial and fungal infections and is characterized by an absence of ROS production due to a deficiency in one of the components of the NADPH oxidase (Meischl and Roos, 1998; Kannengiesser et al, 2008)

  • The phagocyte NADPH oxidase consists of several proteins that are separated between membranes and cytosol in resting cells (Chanock et al, 1994; Babior 1999; El Benna et al, 2005)

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Summary

Introduction

Phagocytes such as polymorphonuclear neutrophils, eosinophils, monocytes and macrophages constitute one of the most powerful means of host defense against bacteria and fungi (Segal, 2005; Nathan, 2006). The phagocyte NADPH oxidase and ROS production play a key role in host defense against microbial pathogens as illustrated by a human genetic disorder called chronic granulomatous disease (CGD), which is associated with life-threatening bacterial and fungal infections and is characterized by an absence of ROS production due to a deficiency in one of the components of the NADPH oxidase (Meischl and Roos, 1998; Kannengiesser et al, 2008).

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