Chronic granulomatous disease--pieces of a cellular and molecular puzzle.
Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes are unable to manufacture microbicidal oxidants. The disorder may be classified into subtypes depending upon the mode of transmission (X-linked or autosomal recessive) and the presence or absence of a heme protein designated 'cytochrome b558' (see below). Patients with CGD suffer recurrent deep-seated bacterial infections that respond poorly to therapy, slowly destroy affected tissues and eventually claim the patients' lives. Clinical deterioration is slowed, though not stopped, by the current practice of placing CGD patients on prophylactic antibiotics. Microbicidal oxidant production fails in CGD because of a defect in the enzyme responsible for the production of superoxide (O2-), the single precursor from which all the microbicidal oxidants ultimately arise. This enzyme, the respiratory burst oxidase, is a membrane-bound oxidase that catalyses the one-electron reduction of oxygen to O2- at the expense of NADPH. The oxidase is dormant in resting phagocytes, but comes to life when the phagocytes are exposed to bacteria or other appropriate stimuli. Components related to the respiratory burst oxidase include cytochrome b558 (one of those subunits has recently been shown to be encoded by a gene that is defective in the most common form of CGD), a flavoprotein that participates directly in O2- production, a cytosolic factor needed for the activation of the oxidase, and a group of 48K phosphoproteins. How these components relate to each other and to the O2- -forming activity of the oxidase is currently under active investigation.
Babior
B M
BM
Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Curnutte
J T
JT
D006105:Granulomatous Disease, Chronic / Q000503:physiopathology*; D006801:Humans