The chemokine CCL18 characterises Pseudomonas infections in cystic fibrosis Lung disease
The chemokine CCL18 characterises Pseudomonas infections in cystic fibrosis Lung disease
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DOI：
10.1183/09031936.00070014
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发表时间：
2014-12-01
影响因子：
24.3
通讯作者：
Hart, Dominik
中科院分区：
文献类型：
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作者：
Hector, Andreas;Kroener, Carolin;Hart, Dominik
囊性纤维化（CF）肺病的特征是慢性铜绿假单胞菌感染和白细胞浸润。趋化因子将白细胞募集到感染部位。基因表达分析发现趋化因子 CCL18 在 CF 白细胞中上调。我们假设CCL18是CF肺部疾病患者感染和炎症的特征。因此，我们定量了CF患者和健康对照者血清和气道液中的CCL18蛋白水平，并离体研究了气道细胞产生的CCL18蛋白。这些研究表明，与健康对照者相比，CF患者血清和气道液中CCL18水平升高。在 CF 患者中，铜绿假单胞菌感染的 CF 患者中 CCL18 水平升高。气道中的 CCL18 水平（而非血清中）与 CF 中肺阻塞的严重程度相关。与未感染铜绿假单胞菌的 CF 患者或健康对照的气道细胞相比，从铜绿假单胞菌感染的 CF 患者中分离出的气道细胞产生的 CCL18 蛋白含量显着更高。 总的来说，这些研究表明，CCL18 水平是 CF 患者慢性铜绿假单胞菌感染和肺阻塞的特征。因此，CCL18 可能作为 CF 肺病的潜在生物标志物和治疗靶点。
Cystic fibrosis (CF) lung disease is characterised by chronic Pseudomonas aeruginosa infection and leukocyte infiltration. Chemokines recruit leukocytes to sites of infection. Gene expression analysis identified the chemokine CCL18 as upregulated in CF leukocytes. We hypothesised that CCL18 characterises infection and inflammation in patients with CF lung disease.Therefore, we quantified CCL18 protein levels in the serum and airway fluids of CF patients and healthy controls, and studied CCL18 protein production by airway cells ex vivo.These studies demonstrated that CCL18 levels were increased in the serum and airway fluids from CF patients compared with healthy controls. Within CF patients, CCL18 levels were increased in P. aeruginosa-infected CF patients. CCL18 levels in the airways, but not in serum, correlated with severity of pulmonary obstruction in CF. Airway cells isolated from P. aeruginosa-infected CF patients produced significantly higher amounts of CCL18 protein compared with airway cells from CF patients without P. aeruginosa infection or healthy controls.Collectively, these studies show that CCL18 levels characterise chronic P. aeruginosa infection and pulmonary obstruction in patients with CF. CCL18 may, thus, serve as a potential biomarker and therapeutic target in CF lung disease.