Nitrogen redox balance in the cystic fibrosis airway - Effects of antipseudomonal therapy
Nitrogen redox balance in the cystic fibrosis airway - Effects of antipseudomonal therapy
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DOI：
10.1164/ajrccm.165.3.2106006
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发表时间：
2002-02-01
影响因子：
24.7
通讯作者：
Goldberg, JB
中科院分区：
文献类型：
--
作者：
Gaston, B;Ratjen, F;Goldberg, JB
反硝化细菌通过同化和异化途径代谢氮氧化物，这些氧化还原反应可能影响肺生理。我们推测，反硝化细菌在呼吸道的定植可以改变囊性纤维化(CF)呼吸道的氮平衡。我们检测了CF患者在抗菌治疗前后的呼吸道氮氧化还原种类。此外，我们还研究了铜绿假单胞菌临床分离株在体外和体外CF痰中的氨(NH4+)和一氧化氮(NO)代谢。治疗后痰和气管抽吸物中的氨浓度均降低。铜绿假单胞菌临床分离株存在一氧化氮合酶(NOR)，既产生NH4+，又消耗NO。此外，妥布霉素体外抑制肺泡灌洗液对NO的消耗。我们的结论是，治疗假单胞性肺部感染与降低CF呼吸道中的NH4+浓度有关。在上皮细胞中，NH4+抑制氯的转运，而氮氧化物抑制阿米洛利敏感的钠转运并增强氯的转运。我们推测，气道氮氧化还原平衡的正常化可能有助于抗假单胞菌治疗对CF肺功能的有利影响。
Denitrifying bacteria metabolize nitrogen oxides through assimilatory and dissimilatory pathways, These redox reactions may affect lung physiology. We hypothesized that airway colonization with denitrifying bacteria could alter nitrogen balance in the cystic fibrosis (CF) airway. We measured airway nitrogen redox species before and after antimicrobial therapy for Pseudomonas aeruginosa in patients with CF. We also studied ammonium (NH4+) and nitric oxide (NO) metabolism in clinical strains of P. aeruginosa in vitro and in CF sputum ex vivo. Ammonium concentrations in both sputum and tracheal aspirates decreased with therapy. Nitric oxide reductase (NOR) was present in clinical strains of A aeruginosa, which both produced NH4+ and consumed NO. Further, NO consumption by CF sputum was inhibited by tobramycin ex vivo. We conclude that treatment of pseudomonal lung infections is associated with decreased NH4+ concentrations in the CF airways. In epithelial cells, NH4+ inhibits chloride transport, and nitrogen oxides inhibit amiloride-sensitive sodium transport and augment chloride transport. We speculate that normalization of airway nitrogen redox balance could contribute to the beneficial effects of anti-pseudomonal therapy on lung function in CF.