Absence of Cytochrome b-245in Chronic Granulomatous Disease

作者：Anthony Walter Segal, Andrew R. Cross, Rodolfo C. Garcia, Niels Borregaard, Niels Henrik Valerius, John F. Soothill, Owen T.G. Jones · 发表于：New England Journal of Medicine · 年份：1983 · DOI：10.1056/nejm198302033080503 · 被引用次数：300 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Vitamin C and Antioxidants Research、Redox biology and oxidative stress

The heme-containing protein cytochrome b-245 has been proposed as a primary component of the microbicidal oxidase system of phagocytes that normally generates superoxide-free radicals but when defective is associated with chronic granulomatous disease. We measured this cytochrome in granulocytes from 27 patients with chronic granulomatous disease and from 64 members of their families. It was undetectable in all 19 of the men in whom the defect appeared to be located on the X chromosome. Female relatives who were heterozygous carriers had reduced concentrations of the cytochrome and variable proportions of cells that were unable to generate superoxide; these two characteristics were closely related (r = 0.93 in the 16 mothers and 0.85 in all 24 carriers, P less than 0.001). In contrast, in all eight patients (seven women) with a probable autosomal recessive inheritance the cytochrome was present but nonfunctional. The properties tested, including midpoint potential, carbon monoxide binding, and organelle distribution, were normal, but the cytochrome did not undergo reduction on cellular stimulation. Thus, absence or malfunction of the cytochrome b-245 may be the causal molecular defect in chronic granulomatous disease, implicating it in the microbicidal oxidase system.