| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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
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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
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