Abstract
Methods: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB.
Results: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1ß. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles.
Conclusions: These results indicate that ß-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.
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- Ashitani J., Mukae H., Hiratsuka T., Nakazato M., Kumamoto K., Matsukura S. Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection. Chest. 2001 Apr;119(4):1131–1137. doi: 10.1378/chest.119.4.1131. [DOI] [PubMed] [Google Scholar]
- Ashitani J., Mukae H., Nakazato M., Ihi T., Mashimoto H., Kadota J., Kohno S., Matsukura S. Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis. Eur Respir J. 1998 Jan;11(1):104–111. doi: 10.1183/09031936.98.11010104. [DOI] [PubMed] [Google Scholar]
- Bals R. Epithelial antimicrobial peptides in host defense against infection. Respir Res. 2000 Oct 20;1(3):141–150. doi: 10.1186/rr25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bals R., Wang X., Wu Z., Freeman T., Bafna V., Zasloff M., Wilson J. M. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest. 1998 Sep 1;102(5):874–880. doi: 10.1172/JCI2410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bensch K. W., Raida M., Mägert H. J., Schulz-Knappe P., Forssmann W. G. hBD-1: a novel beta-defensin from human plasma. FEBS Lett. 1995 Jul 17;368(2):331–335. doi: 10.1016/0014-5793(95)00687-5. [DOI] [PubMed] [Google Scholar]
- Boucher R. C. Human airway ion transport. Part one. Am J Respir Crit Care Med. 1994 Jul;150(1):271–281. doi: 10.1164/ajrccm.150.1.8025763. [DOI] [PubMed] [Google Scholar]
- García J. R., Krause A., Schulz S., Rodríguez-Jiménez F. J., Klüver E., Adermann K., Forssmann U., Frimpong-Boateng A., Bals R., Forssmann W. G. Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J. 2001 Aug;15(10):1819–1821. [PubMed] [Google Scholar]
- Goldman M. J., Anderson G. M., Stolzenberg E. D., Kari U. P., Zasloff M., Wilson J. M. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell. 1997 Feb 21;88(4):553–560. doi: 10.1016/s0092-8674(00)81895-4. [DOI] [PubMed] [Google Scholar]
- Harder J., Bartels J., Christophers E., Schroder J. M. Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 2000 Nov 20;276(8):5707–5713. doi: 10.1074/jbc.M008557200. [DOI] [PubMed] [Google Scholar]
- Harder J., Bartels J., Christophers E., Schröder J. M. A peptide antibiotic from human skin. Nature. 1997 Jun 26;387(6636):861–861. doi: 10.1038/43088. [DOI] [PubMed] [Google Scholar]
- Harder J., Meyer-Hoffert U., Teran L. M., Schwichtenberg L., Bartels J., Maune S., Schröder J. M. Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol. 2000 Jun;22(6):714–721. doi: 10.1165/ajrcmb.22.6.4023. [DOI] [PubMed] [Google Scholar]
- Harwig S. S., Ganz T., Lehrer R. I. Neutrophil defensins: purification, characterization, and antimicrobial testing. Methods Enzymol. 1994;236:160–172. doi: 10.1016/0076-6879(94)36015-4. [DOI] [PubMed] [Google Scholar]
- Hiratsuka T., Nakazato M., Date Y., Ashitani J., Minematsu T., Chino N., Matsukura S. Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia. Biochem Biophys Res Commun. 1998 Aug 28;249(3):943–947. doi: 10.1006/bbrc.1998.9239. [DOI] [PubMed] [Google Scholar]
- Hiratsuka T., Nakazato M., Ihi T., Minematsu T., Chino N., Nakanishi T., Shimizu A., Kangawa K., Matsukura S. Structural analysis of human beta-defensin-1 and its significance in urinary tract infection. Nephron. 2000 May;85(1):34–40. doi: 10.1159/000045627. [DOI] [PubMed] [Google Scholar]
- Homma H., Yamanaka A., Tanimoto S., Tamura M., Chijimatsu Y., Kira S., Izumi T. Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest. 1983 Jan;83(1):63–69. doi: 10.1378/chest.83.1.63. [DOI] [PubMed] [Google Scholar]
- Kadota J., Mukae H., Tomono K., Kohno S. High concentrations of beta-chemokines in BAL fluid of patients with diffuse panbronchiolitis. Chest. 2001 Aug;120(2):602–607. doi: 10.1378/chest.120.2.602. [DOI] [PubMed] [Google Scholar]
- Kadota J., Sakito O., Kohno S., Sawa H., Mukae H., Oda H., Kawakami K., Fukushima K., Hiratani K., Hara K. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Jan;147(1):153–159. doi: 10.1164/ajrccm/147.1.153. [DOI] [PubMed] [Google Scholar]
- Kudoh S., Azuma A., Yamamoto M., Izumi T., Ando M. Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1829–1832. doi: 10.1164/ajrccm.157.6.9710075. [DOI] [PubMed] [Google Scholar]
- Mukae H., Hirota M., Kohno S., Komori K., Fukushima K., Hiratani K., Kadota J., Hara K. Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Sep;148(3):744–751. doi: 10.1164/ajrccm/148.3.744. [DOI] [PubMed] [Google Scholar]
- Mukae H., Kadota J., Ashitani J., Taniguchi H., Mashimoto H., Kohno S., Matsukura S. Elevated levels of soluble adhesion molecules in serum of patients with diffuse panbronchiolitis. Chest. 1997 Dec;112(6):1615–1621. doi: 10.1378/chest.112.6.1615. [DOI] [PubMed] [Google Scholar]
- Mukae H., Kadota J., Kohno S., Kusano S., Morikawa T., Matsukura S., Hara K. Increase in activated CD8+ cells in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis. Am J Respir Crit Care Med. 1995 Aug;152(2):613–618. doi: 10.1164/ajrccm.152.2.7633715. [DOI] [PubMed] [Google Scholar]
- Schröder J. M., Harder J. Human beta-defensin-2. Int J Biochem Cell Biol. 1999 Jun;31(6):645–651. doi: 10.1016/s1357-2725(99)00013-8. [DOI] [PubMed] [Google Scholar]
- Singh P. K., Jia H. P., Wiles K., Hesselberth J., Liu L., Conway B. A., Greenberg E. P., Valore E. V., Welsh M. J., Ganz T. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14961–14966. doi: 10.1073/pnas.95.25.14961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valore E. V., Park C. H., Quayle A. J., Wiles K. R., McCray P. B., Jr, Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest. 1998 Apr 15;101(8):1633–1642. doi: 10.1172/JCI1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang D., Chertov O., Bykovskaia S. N., Chen Q., Buffo M. J., Shogan J., Anderson M., Schröder J. M., Wang J. M., Howard O. M. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999 Oct 15;286(5439):525–528. doi: 10.1126/science.286.5439.525. [DOI] [PubMed] [Google Scholar]
- Zucht H. D., Grabowsky J., Schrader M., Liepke C., Jürgens M., Schulz-Knappe P., Forssmann W. G. Human beta-defensin-1: A urinary peptide present in variant molecular forms and its putative functional implication. Eur J Med Res. 1998 Jul 20;3(7):315–323. [PubMed] [Google Scholar]