THE RESPIRATORY BURST OXIDASE AND THE MOLECULAR-BASIS OF CHRONIC GRANULOMATOUS-DISEASE
THE RESPIRATORY BURST OXIDASE AND THE MOLECULAR-BASIS OF CHRONIC GRANULOMATOUS-DISEASE
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DOI：
10.1002/ajh.2830370410
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发表时间：
1991-08-01
影响因子：
12.8
通讯作者：
BABIOR, BM
中科院分区：
文献类型：
--
作者：
BABIOR, BM
慢性肉芽肿病（CGD）是一种以复发性严重细菌和真菌感染为特征的吞噬细胞功能遗传性疾病，通常始于儿童早期。这些感染通常是由金黄色葡萄球菌或肠杆菌引起的，很难治疗。在早期，CGD患者通常在第一个或第二个十年死于无法控制的败血症。随着抗生素预防CGD的引入，疾病的进程发生了变化，预期寿命更长，住院次数减少，但由于不完全抑制感染引起的并发症更多，包括空心器官狭窄和肺部的缓慢破坏，以及更多的真菌疾病，特别是曲霉。最近，抗生素预防和长期y-干扰素的组合已被采用作为CGD的治疗方法，这一变化有望极大地改善这种疾病患者的前景。最近对CGD的临床方面进行了综述[1]。CGD吞噬细胞的基本问题是它们不能表达呼吸爆发。这是专业吞噬细胞的代谢事件特征，导致产生高活性氧化剂，被吞噬细胞用作杀微生物剂。每当吞噬细胞受到适当的刺激时，呼吸爆发就会发生，其特征是产生大量的超氧化物（02J和H202），并伴随着氧摄取（为02和H202的生成提供氧气）和单磷酸己糖分流活性（细胞的NADPH来源）的急剧增加。在临床实验室，呼吸爆发通常通过NBT试验来检测，该试验在硝酸蓝四氮唑（一种水溶性黄色染料）存在下激活中性粒细胞。在这些条件下，正常的中性粒细胞产生02-，将NBT转化为深蓝色的不溶性物质，但CGD细胞不会产生02-，因此染料保持不变。呼吸爆发的关键是呼吸爆发氧化酶，一种休眠的膜相关酶
Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function characterized by recurrent severe bacterial and fungal infections that usually begin in early childhood. These infections, most frequently due to Staphylococcus aureus or an enterobacillus, are very difficult to treat. In earlier days, CGD patients usually died during the first or second decade from uncontrollable sepsis. With the introduction of antibiotic prophylaxis for CGD, the course of the disease changed, with a longer life expectancy and fewer hospitalizations but more complications from imperfectly suppressed infections, including strictures of hollow organs and slow destruction of the lungs, and more fungal disease, particularly from Aspergillus. Very recently, the combination of antibiotic prophylaxis and long-term y-interferon has been adopted as the treatment for CGD, a change that promises to effect a great improvement in the outlook for patients with this disorder. The clinical aspects of CGD have recently been reviewed [l]. The basic problem with CGD phagocytes is that they are unable to express the respiratory burst. This is a metabolic event characteristic of professional phagocytes' that results in the production of highly reactive oxidizing agents used by the phagocytes as microbicidal agents. The respiratory burst occurs whenever phagocytes are exposed to an appropriate stimulus and is defined by the production of large amounts of superoxide (02J and H202, accompanied by sharp increases in oxygen uptake (supplying the oxygen from which 02-and H202 are made) and hexose monophosphate shunt activity (the cell's source of NADPH). In the clinical laboratory, the respiratory burst is usually detected by the NBT test, a test in which neutrophils are activated in the presence of nitroblue tetrazolium, a water-soluble yellow dye. Under these conditions, normal neutrophils generate 02-, which converts NBT to a dark blue insoluble material, but CGD cells do not generate 02-and therefore leave the dye unchanged. The key to the respiratory burst is the respiratory burst oxidase, a membrane-associated enzyme that is dormant