Regulation of the Phagocyte NADPH Oxidase by Rac GTPase

Phagocytic leukocytes generate reactive oxygen species important for the killing of invading microorganisms. The source of these oxidants is the NADPH oxidase, a tightly controlled multicomponent enzyme made up of a membrane-associated catalytic moiety and cytosolic regulatory components that must assemble to form the active oxidase. The phagocyte NADPH oxidase was the first mammalian system shown to be directly regulated by a Rac GTPase. We review here our understanding of NADPH oxidase regulation by Rac, as well as the regulation of Rac itself, in phagocytic leukocytes. Rather than viewing Rac as a "cog" in the NADPH oxidase machinery, we argue for a view of Rac GTPases as critical "molecular switches" regulating the formation of ROS by phagocytic leukocytes under physiologic and pathologic conditions.