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. CONCLUSION:This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

journal_name

Respir Res

journal_title

Respiratory research

authors

Yanagi S,Ashitani J,Ishimoto H,Date Y,Mukae H,Chino N,Nakazato M

doi

10.1186/1465-9921-6-130

keywords:

subject

Has Abstract

pub_date

2005-11-04 00:00:00

pages

130

eissn

1465-9921

issn

1465-993X

pii

1465-9921-6-130

journal_volume

6

pub_type

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