Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation
Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation
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DOI：
10.1183/09031936.00089709
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发表时间：
2010-06-01
影响因子：
24.3
通讯作者：
Condliffe, A. M.
中科院分区：
文献类型：
--
作者：
McKeon, D. J.;Cadwallader, K. A.;Condliffe, A. M.
先前的研究已经确定了囊性纤维化（CF）中中性粒细胞氧化反应的异常，但尚不清楚这种变化是否与囊性纤维化跨膜传导调节因子（CFTR）的丢失或该疾病中存在的炎症环境有关。本研究的目的是确定CF患者的中性粒细胞是否表现出呼吸爆发的内在异常。采用化学发光法和细胞色素C减少法对稳定的δ F508纯合子CF患者和匹配的健康对照中分离的中性粒细胞的呼吸爆发活性进行了量化。采用Western blotting和RT-PCR检测NADPH氧化酶组分和CFTR的表达。来自CF的中性粒细胞在响应受体连接和颗粒刺激时的氧化输出与对照组没有差异。NADPH氧化酶组分在CF和非CF中性粒细胞中的表达相同。虽然在正常的人中性粒细胞中可以检测到低水平的CFTR mRNA，但我们无法在人中性粒细胞裂解物或免疫沉淀物中检测到CFTR蛋白。CFTR对中性粒细胞氧化活性无控制作用；先前报道的CF和非CF受试者之间中性粒细胞功能的差异很可能与分离细胞的炎症环境有关。
Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst.The respiratory burst activity of neutrophils isolated from stable Delta F508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR.The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates.CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.