Mechanisms of NADPH oxidase activation: translocation of p40phox, rac 1 and rac 2 from the cytosol to the membranes in human neutrophils lacking p47phox or p67phox.

On neutrophil stimulation, the cytosolic components of NADPH oxidase, p67-phox, p47-phox, p40-phox, as well as the Ras-related G-proteins Rac1 and Rac2, are translocated from the cytosol to cell membranes where they associate with a flavocytochrome b, forming a functional complex responsible for the production of oxygen radicals in phagocytes. In this paper we show that (a) in neutrophils from a patient with a form of chronic granulomatous disease (CGD) in which p67-phox is absent, p47-phox and Rac2, but not p40-phox and Rac1 were translocated from the cytosol to the membrane on stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA); (b) in neutrophils from a patient with a form of CGD in which p47-phox is absent, p67-phox, p40-phox and Rac1 failed to associate with the membrane on stimulation with fMLP or PMA, whereas Rac2 was translocated as in normal neutrophils. We also show that in neutrophils from a patient lacking p67-phox, the amount of cytosolic p40-phox was decreased by about 40%. These findings indicate that, on neutrophil stimulation, p67-phox mediates the translocation of p40-phox and Rac1 from the cytosol to cell membranes and that Rac2 associates with the membranes independently of p47-phox and p67-phox.