Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis
Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis
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DOI：
10.1136/thx.2009.114512
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发表时间：
2010-01-01
期刊：
影响因子：
10
通讯作者：
Jensen, P. O.
中科院分区：
文献类型：
--
作者：
Kolpen, M.;Hansen, C. R.;Jensen, P. O.
背景：慢性铜绿假单胞菌肺部感染是囊性纤维化（CF）患者最严重的并发症。这种感染的特征是支气管内粘液样生物膜被许多多形核白细胞（PMN）包围。粘液样表型提供了针对PMN的保护，通常认为PMN会引起主动呼吸爆发，导致肺组织恶化。然而，在慢性感染CF患者的支气管内分泌物中，先前尚未证实中性粒细胞的持续呼吸爆发。基于感染CF支气管中粘液中分子氧（O-2）耗尽的累积证据，有人假设O-由于O-2还原为超氧阴离子（O-2（-）），方法：采用吞噬细胞NADPH氧化酶（Phox）对慢性肺炎患者新鲜痰液中的氧呼吸和呼吸爆发消耗的O-2进行分离。用二苯基碘鎓（DPI）抑制Phox延迟了O-2的消耗，几乎消除了氢乙啶对产生O-2（-）的PMNs的染色，并抑制了痰液中鲁米诺快速增强的化学发光。结论：CF患者痰液中PMNs消耗O-2产生O-2（-），提示CF患者肺内O-2（-）的形成导致呼吸爆发的进行，并加速O-2的消耗。
Background: Chronic lung infection with Pseudomonas aeruginosa is the most severe complication for patients with cystic fibrosis (CF). This infection is characterised by endobronchial mucoid biofilms surrounded by numerous polymorphonuclear leucocytes (PMNs). The mucoid phenotype offers protection against the PMNs, which are in general assumed to mount an active respiratory burst leading to lung tissue deterioration. An ongoing respiratory burst by the PMNs has, however, not been demonstrated previously in endobronchial secretions from chronically infected patients with CF.Objective: Based on the accumulating evidence for depletion of molecular oxygen (O-2) in the mucus in infected CF bronchi, it was hypothesised that the O-2 depletion in the mucus in infected CF bronchi may be accelerated by the respiratory burst of the PMNs due to the reduction of O-2 to the superoxide anion (O-2(-)) by the phagocyte NADPH oxidase (Phox).Methods: Methods were established to isolate the O-2 consumption by the respiratory burst from aerobic respiration in freshly expectorated sputum from chronically infected patients with CF.Results: Inhibition of the Phox with diphenylene iodonium (DPI) delayed O-2 depletion, nearly abolished staining of O-2(-)-producing PMNs with hydroethidine and inhibited the rapid luminol-enhanced chemiluminescence in sputum. Furthermore, the total O-2 consumption was correlated to the concentration of PMNs in the sputum samples.Conclusion: The results demonstrate that CF sputum contains PMNs with an active consumption of O-2 for O-2(-) production and suggest that the respiratory burst is ongoing and causes accelerated O-2 depletion due to formation of O-2(-) in the lungs of chronically infected patients with CF.