Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs.
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 micrograms/ml) and Escherichia coli D31 (MIC of 16 micrograms/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.
Bals
R
R
Institute for Human Gene Therapy, Department of Medicine and Molecular and Cellular Engineering, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Wang
X
X
Meegalla
R L
RL
Wattler
S
S
Weiner
D J
DJ
Nehls
M C
MC
Wilson
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology; D001483:Base Sequence; D023082:Defensins; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004927:Escherichia coli Infections / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D016415:Sequence Alignment
D000890:Anti-Infective Agents; D023082:Defensins; D011506:Proteins