Monocyte/macrophage-Specific NADPH Oxidase Contributes to Antimicrobial Host Defense in X-CGD
Monocyte/macrophage-Specific NADPH Oxidase Contributes to Antimicrobial Host Defense in X-CGD
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单核细胞/巨噬细胞特异性 NADPH 氧化酶有助于 X-CGD 中的抗菌宿主防御
DOI：
10.1007/s10875-015-0138-4
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
and Tadashi Ariga
中科院分区：
文献类型：
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作者：
Yuka Okura;Masafumi Yamada;Futoshi Kuribayashi;Ichiro Kobayashi;and Tadashi Ariga
背景：慢性肉芽肿病（CGD）是一种以细菌和真菌感染易感性为特征的原发性免疫缺陷疾病。编码吞噬细胞烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶gp91phox亚基的incyb基因的各种突变可损害所有类型吞噬细胞的呼吸爆发，导致x -连锁CGD （X-CGD）。目的：我们在这里试图评估X-CGD患者表型减弱的潜在原因。患者为31岁男性，在1岁时因硝基蓝四氮唑还原缺失和acybb突变而被诊断为X-CGD。他在婴儿期克服了反复的细菌感染，身体一直很好。方法采用多态核白细胞（PMNs）和单核/巨噬细胞（单核/巨噬细胞）检测cybbgene基因组DNA、NADPH氧化酶残留活性和gp91phoxin表达。结果尽管在PMNs和单核细胞中都发现了潜在的种系突变，即cybb基因中的c.1016C>A (p.P339H)，但gp91phox在单核细胞/巨噬细胞中的表达和功能活性保持不变，与PMNs明显减少形成鲜明对比。结论在X-CGD婴儿期，PMNs中残余活性氧中间体（ROI）的产生发挥了重要作用，但此后单核/巨噬细胞的功能保留可能弥补了NADPH氧化酶缺陷的PMNs的功能，可能是预测X-CGD患者预后的重要参数。
BackgroundChronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. Various mutations inCYBBencoding the gp91phoxsubunit of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase impair the respiratory burst of all types of phagocytic cells and result in X-linked CGD (X-CGD).PurposeWe here sought to evaluate the underlying cause in an attenuated phenotype in an X-CGD patient. The patient is a 31-year-old male who had been diagnosed as having X-CGD based on the absence of nitroblue tetrazolium reduction and the presence of aCYBBmutation at the age of 1 year. He has been in good health after overcoming recurrent bacterial infections in infancy.MethodsWe investigated genomic DNA analysis ofCYBBgene, residual activity of NADPH oxidase, and expression of gp91phoxin both polymorphonuclear leukocytes (PMNs) and monocytes/macrophages in the present patient.ResultsAlthough his underlying germline mutation, c.1016C>A (p.P339H) in theCYBBgene, was identified in both PMNs and monocytes, the expression and functional activity of gp91phoxretained in monocytes/macrophages, in stark contrast to markedly reduced PMNs.ConclusionsOur results indicate that residual reactive oxygen intermediates (ROI) production in PMNs plays an important role in infantile stage in X-CGD, but thereafter retained function of monocytes/macrophages might compensate for the function of NADPH oxidase deficient PMNs and might be an important parameter for predicting the prognosis of X-CGD patients.