Composition and organization of the NADPH oxidase of phagocytes and other cells.

Introduction Superoxide (OLo-) is produced by phagocytic leukocytes in response to a variety of stimuli. The activation of 0,' production by neutrophils following binding by plasma membrane receptors of the phagocyte to opsonized bacteria or to peptides from degraded bacteria is of great importance. The 0,'and its reaction products contribute to the microbicidal activities of these cells, and so resistance to infection. In the rare genetic disease, chronic granulomatous disease (CGD), neutrophils lack one or more of the protein components of the 02'-generating oxidase and patients suffer repeated infections, demonstrating the involvement of the oxidase in combating infection [ 1, la]. The oxidase that is located in the plasma membrane uses cytosolic NADPH as electron donor and so is known as the NADPH oxidase. It contains a low potential cytochrome b and FAD [2]. Comparison of its sequence with that of other flavoproteins suggests that the FAD-binding site may be on the cytochrome b itself [3]. The cytochrome b is a heterodimer with subunits with M,s of approx. 91 kDa (/I subunit) and 22 kDa ( a subunit) [4, 4a]. The low oxidation/reduction potential of the cytochrome b (Em,,= -245 mV) is suited to its function in an electron transport system linked to