Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
J Cyst Fibros. 2010 May;9(3):217-27. doi: 10.1016/j.jcf.2010.03.001. Epub 2010 Mar 29.
In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli.
Lung tissue from 14 CF patients and four healthy individuals was analyzed for numbers of effector cells, elastin and collagen concentrations, inflammatory markers and density of Pseudomonas aeruginosa. Additionally, desmosine and isodesmosine concentrations were determined in 52 urine specimens from CF patients to estimate the burden of elastase activities in respiratory secretions.
Elastin concentration was significantly decreased and collagen significantly increased in CF alveolar tissues as compared to age-matched, healthy individuals. Elastin split products were significantly increased in urine samples from patients with CF and correlated inversely with age, indicating local tissue remodelling due to elastin degradation by unopposed proteolytic enzymes. Alveolar inflammation was also characterized by a significant cell infiltration of neutrophils, macrophages and T cells, extensive nuclear factor-kappaB and insulin-like growth factor-1 activation in various cell types and increased intercellular adhesion molecule-1 expression, and increased numbers of myofibroblasts. Additionally, ceramide accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli.
Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies.
在囊性纤维化（CF）患者的感染肺部中，机会性病原体和突变的囊性纤维化跨膜电导调节蛋白（CFTR）导致慢性气道炎症，其特征是中性粒细胞/巨噬细胞浸润、细胞因子释放和神经酰胺积累。我们试图研究肺泡中的 CF 肺部炎症。
分析了 14 名 CF 患者和 4 名健康个体的肺组织中效应细胞的数量、弹性蛋白和胶原蛋白浓度、炎症标志物和铜绿假单胞菌的密度。此外，还测定了 52 份 CF 患者尿液标本中的脱亚氨酸和异脱亚氨酸浓度，以估计呼吸道分泌物中弹性酶活性的负担。
与年龄匹配的健康个体相比，CF 肺泡组织中的弹性蛋白浓度显著降低，胶原蛋白显著增加。CF 患者尿液样本中的弹性蛋白分解产物显著增加，并与年龄呈负相关，表明由于未被蛋白酶抑制的弹性酶降解，导致局部组织重塑。肺泡炎症还表现为中性粒细胞、巨噬细胞和 T 细胞的显著细胞浸润，各种细胞类型中核因子-κB 和胰岛素样生长因子-1 的广泛激活，以及细胞间黏附分子-1 表达的增加和肌成纤维细胞数量的增加。此外，神经酰胺在缺乏 CFTR 的 II 型肺泡上皮细胞中积累。在炎症肺泡中很少存在铜绿假单胞菌。
慢性炎症和重塑存在于 CF 肺部的肺泡组织中，需要通过抗炎治疗来解决。
