NADPH oxidase activation in neutrophils: Role of the phosphorylation of its subunits

Abstract

Neutrophils are key cells of innate immunity and during inflammation. Upon activation, they produce large amounts of superoxide anion (O ) and ensuing reactive oxygen species (ROS) to kill phagocytized microbes. The enzyme responsible for O production is called the phagocyte NADPH oxidase. This is a multicomponent enzyme system that becomes active after assembly of four cytosolic proteins (p47 , p67 , p40 and Rac2) with the transmembrane proteins (p22 and gp91 , which form the cytochrome b ). gp91 represents the catalytic subunit of the NADPH oxidase and is also called NOX2. NADPH oxidase-derived ROS are essential for microbial killing and innate immunity; however, excessive ROS production induces tissue injury and prolonged inflammatory reactions that contribute to inflammatory diseases. Thus, NADPH oxidase activation must be tightly regulated in time and space to limit ROS production. NADPH oxidase activation is regulated by several processes such as phosphorylation of its components, exchange of GDP/GTP on Rac2 and binding of p47 and p40 to phospholipids. This review aims to provide new insights into the role of the phosphorylation of the NADPH oxidase components, that is gp91 , p22 , p47 , p67 and p40 , in the activation of this enzyme.

Induction of HO-1 by Mevastatin Mediated via a Nox/ROS-Dependent c-Src/PDGFRα/PI3K/Akt/Nrf2/ARE Cascade Suppresses TNF-α-Induced Lung Inflammation

“…To confirm the role of p47 phox and Nox2 in MVS-induced responses, the protein levels of p47 phox and Nox2 were knocked down by their respective siRNAs and reduced the MVS-induced HO-1 expression in HPAEpiCs ( Figure 4C). Previous studies have shown that phosphorylation of p47 phox leading to NADPH oxidase/ROS-dependent HO-1 expression could protect against the release of inflammatory mediators from HPAEpiCs [19,34]. First, we found that MVS-stimulated phosphorylation of p47 phox was reduced by transfection with p47 phox siRNA ( Figure 5A).…”

Long‐term ethanol consumption promotes changes in β‐defensin isoform gene expression and induces structural changes and oxidative DNA damage to the epididymis of rats

“…According to the literature, infiltrated leukocytes in tissues and their PMNs generate ROS in several ways. ROS production is stimulated by the generation of superoxide anions by phagocyte NADPH oxidase (Belambri et al, ), which is mediated by protein kinase C and raf‐MEK‐ERK activation (Awasthi et al, ). In addition, signals from PMNs result in the release of granule proteases, and the secreted effectors trigger ROS production (Glennon‐Alty, Hackett, Chapman, & Wright, ).…”

GILZ restrains neutrophil activation by inhibiting the MAPK pathway

“…ROS production depends on the activation of NADPH oxidase, an enzymatic system that transfers electrons from cytosolic NADPH to phagolysosomal O 2 to produce superoxide anion (O 2 − ). NADPH oxidase activation leads to respiratory burst, which consists of increased oxygen consumption by neutrophils . In the resting cell, some NADPH oxidase components, such as p40 phox , p47 phox , and p67 phox exist as a complex in the cytosol.…”