Abstract
Neutrophils, a member of leukocytes, phagocytose and kill phathogenic organisms, thereby playing a crucial role in host defense. During phagocytosis, an enzyme called the phagocyte NADPH oxidase becomes activated to produce reactive oxygen species (ROS) that act as microbicidal agents. Activation of the oxidase must be strictly regulated, since ROS have a high reactivity and thus their overproduction causes inflammatory responses. The oxidase activation involves assembly of the cytosolic regulatory proteins p47phox, p67phox, p40phox, and small GTPase Rac with the membrane-integrated cytochrome b558, the catalytic core of the enzyme. Because the assembly requires a variety of protein-protein interactions mediated via modular domains, the knowledge of regulation of these interactions is important for our understanding of the molecular mechanism for the NADPH oxidase activation. On the basis of our current findings, here we discuss the activation mechanism with special attention to the induction and maintenance of the interactions between the oxidase factors.
