Increased concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis
Increased concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis
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DOI：
10.1136/thorax.58.5.425
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发表时间：
2003-05-01
期刊：
影响因子：
10
通讯作者：
Nakazato, M
中科院分区：
文献类型：
--
作者：
Hiratsuka, T;Mukae, H;Nakazato, M
背景：人β-防御素（HBD）-1和-2是存在于呼吸道的抗菌肽。最近的研究表明β-防御素在囊性纤维化中的活性降低，提示β-防御素可能在慢性呼吸道感染的病理过程中起重要作用。弥漫性泛细支气管炎（DPB）是一种进行性疾病，其特征是经常发生叠加感染，通常由铜绿假单胞菌引起。方法：采用放射免疫法测定33例DPB患者和30例正常人血浆和支气管肺泡灌洗液（BAL）中HBD-1和HBD-2的浓度。HBD-2的定位进行了研究，在一个开放的肺活检标本从DPB患者。结果：高浓度的HBD-1和HBD-2注意到从DPB患者的BAL液。与对照组相比，DPB患者的HBD-2血浆浓度升高，但HBD-1没有升高。在DPB患者中，BAL液中HBD-2浓度与从BAL液中回收的细胞数（总细胞、中性粒细胞和淋巴细胞）以及BAL液中IL-1 β浓度显著相关。合成的HBD-2，而不是HBD-1，对铜绿假单胞菌具有剂量依赖性杀菌活性。大环内酯类药物治疗14例患者显着降低BAL液浓度的HBD-2，但不是HBD-1或血浆浓度的HBD-1和HBD-2。肺组织的免疫组化显示HBD-2在远端细支气管上皮细胞的定位。结论：这些结果表明，β-防御素，特别是HBD-2，参与抗菌防御在呼吸道中的DPB，和BAL液浓度的HBD-2可能是一个有用的标记物的DPB患者的气道炎症。
Background: Human beta-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of beta-defensins in cystic fibrosis, suggesting that beta-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease.Methods: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB.Results: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid ( total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1beta. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles.Conclusions: These results indicate that beta-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.