Research of defensins in respiratory infection

呼吸道感染中防御素的研究

• 批准号: 13670607
• 负责人: MUKAE Hiroshi
• 金额: $ 1.54万
• 依托单位: NAGASAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670607/
• 关键词: α-defensins; β-defensin-1; β-defensin-2; diffuse panbronchiolitis; idiopathic pulmonary fibrosis; radioimmunoassay; pulmonary tuberculosis; Mycobacterium avium-intracellulare infection; 肺結核; 非定型抗酸菌症; インターロイキン8; 免疫染色体

Defensins are strongly cationic and antimicrobial peptides. They have broad spectrum microbicidal activities against various Gram positive and Gram negative bacteria, mycobacteria, fungi, and certain enveloped viruses. Human defensins are classified as α- and β-defensins. The human α-defensin family comprises six members four of which are located in the neutrophil. Four b-defensins have also been isolated in humans. Human β-defensin (HBD)-1 is expressed mainly in the urogenital tract. Human HBD-2 is expressed in human skin, trachea and lung. We measured the levels of α-defensins in plasma and bronchoalveolar lavage fluid (BALF) of patients with Mycobacterium avium-intracellulare infection (MAC), pulmonary tuberculosis, and idiopathic pulmonary fibrosis using radioimmunoassay established by us. Plasma concentrations of α-defensins were significantly higher in patients with these diseases. In addition, BALF concentrations of α-defensins were also higher in patients with MAC and pulmonary … More tuberculosis than in healthy subjects. In BALF of patients with MAC and tuberculosis, the concentration of α-defensins correlated positively with the levels of interleukin-8, and higher concentrations of α-defensins in BALF were also detected in patients with cavitary lesions. There was an inverse relationship between plasma α-defensins and the arterial oxygen tension and pulmonary function in these patients. These findings suggest that α-defensins play an important role in the lung involvement of these patients and that the plasma α-defensin level may be a useful marker of disease severity and activity in the diseases. In patients with idiopathic pulmonary fibrosis, positive staining was observed immunohistochemically inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas.We also measured the plasma and BALF concentrations of α-defensins, HBD-1 and HBD-2 in patients with diffuse panbronchiolitis (DPB). High concentrations of α-defensins, HBD-1 and HBD-2 were noted in BALF from patients with DPB. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients, the BALF levels of α-defensins and HBD-2 correlated significantly with the BALF levels of IL-8 and IL-lβ, respectively. These results indicate that β-defensins, particular HBD-2 participate in antimicrobial defence in the respiratory tract in DPB. Less

防御素是一种强阳离子抗菌肽。它们对各种革兰氏阳性和革兰氏阴性细菌、分枝杆菌、真菌和某些包膜病毒具有广谱杀微生物活性。人防御素分为α-防御素和β-防御素。人α-防御素家族由六个成员组成，其中四个位于中性粒细胞中。在人类中也分离出了四种b-防御素。人β-防御素（HBD）-1主要在泌尿生殖道表达。人HBD-2在人皮肤、气管和肺中表达。应用放射免疫法测定了禽分枝杆菌感染（MAC）、肺结核和特发性肺纤维化患者血浆和支气管肺泡灌洗液（BALF）中α-防御素的水平。这些疾病患者的α-防御素血浆浓度显著升高。此外，MAC和肺动脉高压患者BALF中α-防御素的浓度也较高， ...更多信息 结核病比健康人。MAC和肺结核患者BALF中α-防御素水平与IL-8水平呈正相关，空洞性病变患者BALF中α-防御素水平也较高。血浆α-防御素水平与动脉血氧分压和肺功能呈负相关。这些结果表明，α-防御素在这些患者的肺受累中起重要作用，血浆α-防御素水平可能是疾病严重程度和活动性的有用标志。在特发性肺纤维化患者中，肺泡隔内、外中性粒细胞染色呈阳性，尤其在致密纤维化区，我们还检测了弥漫性泛细支气管炎（DPB）患者血浆和BALF中α-防御素、HBD-1和HBD-2的浓度。DPB患者BALF中α-防御素、HBD-1和HBD-2的浓度较高。与对照组相比，DPB患者的HBD-2血浆浓度升高，但HBD-1血浆浓度未升高。患者BALF中α-防御素和HBD-2水平分别与IL-8和IL-1 β水平显著相关。这些结果表明，β-防御素，特别是HBD-2参与DPB呼吸道的抗菌防御。少

项目成果

Jun-ichi Ashitani, Hiroshi Mukae, Takeaki Hiratsuka, Masamitsu Nakazato, et al.: "Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection"Chest. 119・4. 1131-1137 (2001)

Jun-ichi Ashitani、Hiroshi Mukae、Takeaki Hiratsuka、Masamitsu Nakazato 等：“鸟分枝杆菌细胞内感染患者的血浆和 BAL 液浓度”Chest 1131-1137。

Shigeru Katoh, Hiroshi Mukae, et al.: "Characterization of CD44 expression on alveolar macrophages in patients with diffuse panbronchiolitis"Clin Exp Immunol.. 55-5. 223-227 (2001)

Shigeru Katoh、Hiroshi Mukae 等人：“弥漫性全细支气管炎患者肺泡巨噬细胞上 CD44 表达的特征”Clin Exp Immunol.. 55-5。

Takeaki Hiratsuka, Hiroshi Mukae, et al.: "Elevated concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis"Thorax. (In press). (2003)

Takeaki Hiratsuka、Hiroshi Mukae 等人：“弥漫性全细支气管炎患者血浆和支气管肺泡灌洗液中人 β-防御素浓度升高”（出版中）。

Hiroshi Mukae, Masamitsu Nakazato et al.: "Elevated plasma concentrations of α-defensins in patients with idiopathic pulmonary fibrosis"Thorax.. 57-7. 623-628 (2002)

Hiroshi Mukae、Masamitsu Nakazato 等人：“特发性肺纤维化患者的 α-防御素血浆浓度升高”Thorax.. 57-7 (2002)。

Jun-ichi Ashitani, Hiroshi Mukae, et al.: "Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection"Chest.. 119-4. 1131-1137 (2001)

Jun-ichi Ashitani、Hiroshi Mukae 等人：“鸟分枝杆菌胞内感染患者血浆和 BAL 液中抗菌肽的浓度”Chest.. 119-4。