Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
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DOI：
10.1172/jci0213870
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发表时间：
2002-02-01
影响因子：
15.9
通讯作者：
Döring, G
中科院分区：
文献类型：
--
作者：
Worlitzsch, D;Tarran, R;Döring, G
CF发病机制的当前理论预测CF气道内细菌感染的不同诱发“局部环境”条件和部位。在这里，我们表明，在CF患者建立肺部疾病，铜绿假单胞菌位于缺氧粘液脓性肿块在气道腔。体外研究表明，CF特异性增加上皮O-2消耗，增加气道表面液体（ASL）体积吸收和粘液淤滞，产生陡峭的缺氧梯度内增厚的粘液CF上皮表面感染前。沉积在CF气道表面上的活动性铜绿假单胞菌渗透到缺氧粘液区，并以增加的藻酸盐产生对该环境作出反应。随着铜绿假单胞菌在氧限制环境中的生长，局部缺氧加剧，并导致体内检测到的明显厌氧。这些研究表明，CF的新疗法包括去除缺氧粘液斑块和对适应厌氧环境的铜绿假单胞菌有效的抗生素。
Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O-2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.