Research of defensins in respiratory infection

防御素是强阳离子和抗菌肽。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。人体防御素分为α-和β-防御素。人类α-防御素家族包括6个成员，其中4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主要表达于泌尿生殖道。人HBD-2在人体皮肤、气管和肺部均有表达。我们采用自行建立的放射免疫法测定了鸟分枝杆菌胞内感染（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。这些疾病患者血浆α-防御素浓度明显升高。此外，α-防御素的BALF浓度在MAC和肺结核患者中也高于健康人。MAC合并结核患者BALF中α-防御素浓度与白细胞介素-8水平呈正相关，空洞病变患者BALF中α-防御素浓度也较高。血浆α-防御素水平与动脉氧张力、肺功能呈负相关。这些结果提示α-防御素在这些患者的肺部累及中起重要作用，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，肺泡间隔内、外中性粒细胞免疫组化染色呈阳性，特别是在致密纤维化区。我们还测量了弥漫性泛细支气管炎（DPB）患者血浆中α-防御素、HBD-1和HBD-2的浓度和BALF浓度。DPB患者的BALF中存在高浓度的α-防御素、HBD-1和HBD-2。与对照组相比，DPB患者血浆中HBD-2浓度升高，但未发现HBD-1浓度升高。在患者中，α-防御素和HBD-2的BALF水平分别与IL-8和il - 1 β的BALF水平显著相关。这些结果表明β-防御素，特别是HBD-2参与了DPB呼吸道的抗菌防御。少

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