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Infection and Immunity, July 1999, p. 3542-3547, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mouse beta -Defensin 3 Is an Inducible Antimicrobial Peptide Expressed in the Epithelia of Multiple Organs

Robert Bals,1 Xiaorong Wang,1 Rupalie L. Meegalla,1 Sigrid Wattler,2 Daniel J. Weiner,1,3 Michael C. Nehls,2 and James M. Wilson1,*

Institute for Human Gene Therapy, Department of Medicine and Molecular and Cellular Engineering, The Wistar Institute,1 and Division of Pulmonary Medicine, Children's Hospital of Philadelphia,3 Philadelphia, Pennsylvania 19104, and Lexicon Genetics Incorporated, The Woodlands, Texas 773812

Received 5 January 1999/Returned for modification 13 January 1999/Accepted 12 March 1999

One component of host defense at mucosal surfaces is epithelium-derived peptides with antimicrobial activity called defensins. We describe in this report the isolation and characterization of a murine homologue of human beta -defensin 2 (hBD-2) called mouse beta -defensin 3 (mBD-3). The predicted amino acid sequence shows the hallmark features of other known epithelial defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-3 revealed two exons separated by a 1.7-kb intron. The mBD-3 gene is localized at the proximal portion of chromosome 8, the site where genes for mouse alpha - and beta -defensins are found. Under basal condition, mBD-3 transcripts were detected at low levels in epithelial cells of surface organs, such as the intestine and lung. After instillation of Pseudomonas aeruginosa PAO1 into mouse airways, mBD-3-specific mRNA was upregulated significantly not only in large airways but also in the small bowel and liver. Recombinant mBD-3 peptide, produced from a baculovirus expression system, showed antimicrobial activity against P. aeruginosa PAO1 (MIC of 8 µg/ml) and Escherichia coli D31 (MIC of 16 µg/ml) in a salt-dependent manner. This study demonstrates that a murine homologue of hBD-2 is present in the respiratory system and other mucosal surfaces. These similarities between murine and human host defense apparatus provide further impetus to evaluate the mouse as a model for studying the human innate host defense system.

* Corresponding author. Mailing address: 204 Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104-4268. Phone: (215) 898-3000. Fax: (215) 898-6588. E-mail: wilsonjm{at}mail.med.upenn.edu.

Infection and Immunity, July 1999, p. 3542-3547, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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