Chronic granulomatous disease: more than the lack of superoxide?

Chronic granulomatous disease (CGD) is an inherited disease characterized b y severe and recurrent bacterial and fungal infections manifested in most c ases in early childhood, Phagocytic cells of CGD patients are unable to pro duce superoxide anions, and their efficiency in bacterial killing is signif icantly impaired, Recent work has shown alterations in the electrophysiolog ical properties of CGD granulocytes, which might contribute to the pathogen esis of the disease, The new aspects that we discuss in this review concern the proton channel function of gp91(phox) (the electron-transporting subun it of the NADPH oxidase) and the electrogenic activity of the active enzyme complex, which can affect the transmembrane trafficking of several ions. B ased on the reviewed data, we also propose a hypothesis that the absence of a functional NADPH oxidase in CGD neutrophils could result in altered ion compositions within intracellular and intraphagosomal spaces during the pro cess of phagocytosis.