The Respiratory Burst Oxidase and the Molecular Genetics of Chronic Granulomatous Disease

Abstract

The phagocyte respiratory burst oxidase plays a central role in the inflammatory response. This membrane-bound enzyme complex is comprised of both integral membrane and cytosolic proteins and catalyzes the formation of large quantities of superoxide in response to inflammatory stimuli. While superoxide and its oxidant derivatives normally serve a microbicidal function, excessive or inappropriate release of these products contribute to inflammatory tissue injury. Chronic granulomatous disease (CGD) is a group of inherited disorders characterized by an absent neutrophil respiratory burst, which leads to recurrent and often life-threatening infections in affected patients. The analysis of the specific cellular defects in CGD has been instrumental in the identification and characterization of individual oxidase components. Four distinct genetic subgroups are presently recognized, each involving a different protein essential for respiratory burst oxidase function. This article summarizes recent advances in the characterization of the protein components and cellular biochemistry of the respiratory burst oxidase and reviews the classification and molecular genetics of CGD. The application of these findings to new approaches to the diagnosis and treatment of CGD are also reviewed.