Characterisation of the enzyme defect in chronic granulomatous disease.

Strikingly reduced activity of an enzyme, normally located in the plasma membrane of human neutrophils, has been demonstrated in a male patient with chronic granulomatous disease (C.G.D.). The subcellular distribution of N.A.D.H.-dependent reduction of nitroblue tetrazolium (N.B.T.) was determined in neutrophils because reduction of this dye by these patients is grossly impaired. Assayed at high concentrations of N.A.D.H. (1 mmol/1), N.B.T. is reduced by enzymes in the cytosol and mitochondria in addition to the plasma membrane by both normal and C.G.D. cells--properties which previously obscured the identity and location of this enzyme. At a more physiological concentration of N.A.D.H. (25 mumol/1), reduction of the dye by the plasma membrane, the principal site of N.B.T. reduction by normal neutrophils, was absent in the patient with C.G.D. It is suggested that absence or imperfect function of this reductase enzyme is the primary lesion in this disease.