Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils.

ABSTRACT: Neutrophils are critical for the defense against pathogens, in part through the extrusion of extracellular DNA traps, phagocytosis, and the production of reactive oxygen species. Neutrophils may also play an important role in the pathogenesis of rheumatoid arthritis (RA) through the activation of protein arginine deiminases (PADs) that citrullinate proteins that subsequently act as autoantigens. We report that PAD4 is physically associated with the cytosolic subunits of the oxidative burst machinery, p47^phox (also known as neutrophil cytosol factor 1, NCF1) and p67^phox (NCF2). Activation of PAD4 by membranolytic insults that result in high levels of intracellular calcium (higher than physiological neutrophil activation) leads to rapid citrullination of p47^phox

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC6189209 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature