Segal A W, Cross A R, Garcia R C, Borregaard N, Valerius N H, Soothill J F, Jones O T
N Engl J Med. 1983 Feb 3;308(5):245-51. doi: 10.1056/NEJM198302033080503.
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.
含血红素的蛋白质细胞色素b - 245被认为是吞噬细胞杀菌氧化酶系统的主要成分，该系统通常产生超氧自由基，但有缺陷时与慢性肉芽肿病相关。我们检测了27例慢性肉芽肿病患者及其64名家庭成员粒细胞中的这种细胞色素。在所有19名缺陷似乎位于X染色体上的男性中均未检测到。作为杂合子携带者的女性亲属细胞色素浓度降低，且有不同比例的细胞无法产生超氧自由基；这两个特征密切相关（16名母亲中r = 0.93，所有24名携带者中r = 0.85，P小于0.001）。相比之下，在所有8例可能为常染色体隐性遗传的患者（7名女性）中，细胞色素存在但无功能。所检测的特性，包括中点电位、一氧化碳结合和细胞器分布均正常，但细胞色素在细胞受刺激时未发生还原反应。因此，细胞色素b - 245的缺失或功能异常可能是慢性肉芽肿病的致病分子缺陷，表明它参与了杀菌氧化酶系统。
