Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection.
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.
Yanagi
Shigehisa
S
Third Department of Internal Medicine, Miyazaki University School of Medicine, Miyazaki 889-1692, Japan. shigeyana2002@yahoo.co.jp
Ashitani
Jun-ichi
J
Ishimoto
Hiroshi
H
Date
Yukari
Y
Mukae
Hiroshi
H
Chino
Naoyoshi
N
Nakazato
Masamitsu
M
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*
C106641:DEFB4A protein, human; D023083:beta-Defensins