PMID- 16269090 OWN - NLM STAT- MEDLINE DCOM- 20060329 LR - 20181113 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 6 IP - 1 DP - 2005 Nov 4 TI - Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection. PG - 130 AB - 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. FAU - Yanagi, Shigehisa AU - Yanagi S AD - Third Department of Internal Medicine, Miyazaki University School of Medicine, Miyazaki 889-1692, Japan. shigeyana2002@yahoo.co.jp FAU - Ashitani, Jun-ichi AU - Ashitani J FAU - Ishimoto, Hiroshi AU - Ishimoto H FAU - Date, Yukari AU - Date Y FAU - Mukae, Hiroshi AU - Mukae H FAU - Chino, Naoyoshi AU - Chino N FAU - Nakazato, Masamitsu AU - Nakazato M LA - eng PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051104 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (DEFB4A protein, human) RN - 0 (beta-Defensins) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Lung/*metabolism MH - Male MH - Respiratory Tract Infections/*metabolism MH - Up-Regulation MH - beta-Defensins/*metabolism PMC - PMC1298335 EDAT- 2005/11/05 09:00 MHDA- 2006/03/30 09:00 PMCR- 2005/11/04 CRDT- 2005/11/05 09:00 PHST- 2005/07/21 00:00 [received] PHST- 2005/11/04 00:00 [accepted] PHST- 2005/11/05 09:00 [pubmed] PHST- 2006/03/30 09:00 [medline] PHST- 2005/11/05 09:00 [entrez] PHST- 2005/11/04 00:00 [pmc-release] AID - 1465-9921-6-130 [pii] AID - 10.1186/1465-9921-6-130 [doi] PST - epublish SO - Respir Res. 2005 Nov 4;6(1):130. doi: 10.1186/1465-9921-6-130.