title: Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection.
abstract: BACKGROUND
  Human beta-defensin-4 (hBD-4), a new member of the beta-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI) by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF).
  
  
  METHODS
  The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA). Localization of hBD-4 was studied through immunohistochemical analysis (IHC). We investigated the effects of lipopolysaccharide (LPS) on hBD-4 expression and its release from small airway epithelial cells (SAEC). We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA.
  
  
  RESULTS
  hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level.
  
  
  CONCLUSIONS
  This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.
authors.affiliation: Third Department of Internal Medicine, Miyazaki University School of Medicine, Miyazaki 889-1692, Japan. shigeyana2002@yahoo.co.jp
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Yanagi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ashitani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Chino
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D012141:Respiratory Tract Infections / Q000378:metabolism*; D015854:Up-Regulation; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C106641:DEFB4A protein, human; D023083:beta-Defensins