Activation of the NADPH oxidase involves the small GTP-binding protein p21^rac1

PROFESSIONAL phagocytes, such as neutrophils and monocytes, have an NADPH oxidase that generates superoxide and other reduced oxygen species important in killing microorganisms (reviewed in ref. 1). Several components of the oxidase complex have been identified as targets of genetic defects causing chronic granulomatous disease^2-4. The complex consists of an electron transport chain that has as its substrate cytosolic NADPH and which discharges superoxide into the cavity of the intracellular phagocytic vacuole. The only electron transport component identified so far is a low-potential cytochrome b (refs 5,6), apparently the only membrane component required⁷. At least three cytosolic factors are also necessary, two of which, p67^phox and p47^phox, have been identified by their absence in patients with chronic granulomatous disease^8-11. A third component, ω1 (refs 12, 13), is required for stimulation of oxidase activity in a cell-free system^14-16. The active components of purified ω1 are two proteins that associate as heterodimers¹⁷, and here we report that these are the small GTP-binding protein p21^racl and the GDP-dissociation inhibitor rhoGDI.