Expression and antimicrobial function of bactericidal permeability-increasing protein in cystic fibrosis patients
Expression and antimicrobial function of bactericidal permeability-increasing protein in cystic fibrosis patients
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DOI：
10.1128/iai.02066-05
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发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Gessner, Andre
中科院分区：
文献类型：
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作者：
Aichele, Diana;Schnare, Markus;Gessner, Andre
在囊性纤维化（CF）中，限制患儿预后的条件是慢性阻塞性肺疾病伴慢性和持续性感染，主要是铜绿假单胞菌粘液样菌株。大多数CF患者具有抗中性粒细胞胞浆抗体（ANCA），主要针对杀菌性通透性增加蛋白（BPI），可能干扰BPI的抗菌作用。我们分析了CF患者气道中BPI的表达，在痰液或支气管肺泡灌洗标本中，几乎所有患者都表达BPI mRNA和蛋白，细胞内染色和随后的流式细胞术显示，BPI主要是中性粒细胞的产物。重复测量显示，在几个月内，个体BPI表达水平与白细胞介素-8定量相关。体外，从CF患者分离的铜绿假单胞菌启动了BPI的快速释放，独立于蛋白质从头合成。此外，纯化的天然BPI以及27-mer BPI衍生肽对患者来源的粘液样铜绿假单胞菌菌株和对所有抗生素耐药的细菌都显示出抗菌活性。因此，对粘液样铜绿假单胞菌具有功能活性的BPI在CF患者的气道中表达，但可能受到自身抗体的阻碍，导致慢性感染。
In cystic fibrosis (CF), the condition limiting the prognosis of affected children is the chronic obstructive lung disease accompanied by chronic and persistent infection with mostly mucoid strains of Pseudomonas aeruginosa. The majority of CF patients have antineutrophil cytoplasmic antibodies (ANCA) primarily directed against the bactericidal permeability-increasing protein (BPI) potentially interfering with antimicrobial effects of BPI. We analyzed the expression of BPI in the airways of patients with CF. In their sputum samples or bronchoalveolar lavage specimens, nearly all patients expressed BPI mRNA and protein, which were mainly products of neutrophil granulocytes as revealed by intracellular staining and subsequent flow cytometry. Repeated measurements revealed consistent individual BPI expression levels during several months quantitatively correlating with interleukin-8. In vitro, P. aeruginosa isolates from CF patients initiated the rapid release of BPI occurring independently of protein de novo syntheses. Furthermore, purified natural BPI as well as a 27-mer BPI-derived peptide displayed antimicrobial activity against even patient-derived mucoid P. aeruginosa strains and bacteria resistant against all antibiotics tested. Thus, BPI that is functionally active against mucoid P. aeruginosa strains is expressed in the airways of CF patients but may be hampered by autoantibodies, resulting in chronic infection.