Rho GTPases and the control of the oxidative burst in polymorphonuclear leukocytes

Abstract

Stimulation of quiescent leukocytes activates the NADPH oxidase, a membrane-associated enzyme system that generates superoxide and other reactive oxygen species (ROS) that are used to kill bacteria within the phagosome. This chapter describes this multicomponent NADPH oxidase system, one of the first cellular systems shown to be directly regulated by Rac GTPases. We present current models of-NADPH oxidase regulation by Rac2 and describe how Rac2 activation controls the timing of ROS production in adherent neutrophils. The antagonistic role that Cdc42 plays as a competitor of Rac2 for binding to the cytochrome component of the NADPH oxidase is discussed as a possible mechanism for tonic regulation of ROS production during the formation of the phagosome. Finally, we briefly depict mechanisms by which invasive bacteria can alter (inhibit) NADPH oxidase function, focusing on the effects of invasive bacteria on components and assembly of the NADPH oxidase. © Springer-Verlag 2005.