title: Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Neutrophils are thought to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Human neutrophils contain antimicrobial and cytotoxic peptides in the azurophil granules which belong to a family of mammalian neutrophil peptides named alpha-defensins. A study was undertaken to investigate the role of alpha-defensins in the pathogenesis of IPF.
  
  
  METHODS
  The concentrations of alpha-defensins (human neutrophil peptides (HNPs) 1, 2, and 3) in plasma and bronchoalveolar lavage (BAL) fluid of 30 patients with IPF and 15 healthy subjects were measured by radioimmunoassay.
  
  
  RESULTS
  The concentrations of alpha-defensins in plasma, but not in BAL fluid, were significantly higher in IPF patients than in controls. BAL fluid concentrations of interleukin (IL)-8 in patients with IPF, which were significantly higher than in controls, correlated with those of alpha-defensins. An inverse relationship was seen between plasma alpha-defensin levels and the arterial oxygen tension (PaO(2)) and pulmonary function (vital capacity (%VC), forced expiratory volume in 1 second (FEV(1)), and carbon monoxide transfer factor (%TLCO)) in patients with IPF. Plasma levels of alpha-defensins also correlated with the clinical course in IPF patients with an acute exacerbation. Immunohistochemically, positive staining was observed inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas.
  
  
  CONCLUSIONS
  These findings suggest that alpha-defensins play an important role in the pathogenesis of IPF, and that the plasma alpha-defensin level may be a useful marker of disease severity and activity.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. hmukae@net.nagasaki-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Mukae
authors.forename: H
authors.initials: H
authors.lastname: Iiboshi
authors.forename: M
authors.initials: M
authors.lastname: Nakazato
authors.forename: T
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: M
authors.initials: M
authors.lastname: Tokojima
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: J
authors.initials: J
authors.lastname: Ashitani
authors.forename: J
authors.initials: J
authors.lastname: Kadota
authors.forename: S
authors.initials: S
authors.lastname: Matsukura
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002248:Carbon Monoxide / Q000032:analysis; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011510:Proteolipids / Q000097:blood; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000503:physiopathology; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D014797:Vital Capacity / Q000502:physiology; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D010446:Peptide Fragments; D011347:Procollagen; D011510:Proteolipids; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D023084:alpha-Defensins; C041876:procollagen Type III-N-terminal peptide; D002248:Carbon Monoxide