Murine beta-defensin-3 is an inducible peptide with limited tissue expression and broad-spectrum antimicrobial activity.
Beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. Similarities between mammalian beta-defensins may permit the use of murine models to further define the role of these peptides in innate host defense. Murine beta-defensin-3 (mBD-3) is a peptide that exhibits homology at the gene level to human beta-defensin-2 (hBD-2), one of four beta-defensins identified in man. The purpose of this study was to determine the antimicrobial activity of mBD-3, the tissue distribution of mBD-3 expression, and the effect of gram-negative bacterial infection on mBD-3 expression. Based on the sequence deduced from mBD-3 cDNA, a 40-amino acid peptide was assembled using automated [n-(9-fluorenyl)methoxycarbonyl] solid-phase synthesis. The antimicrobial activity of synthetic mBD-3 was evaluated in microdilution broth assays using bacterial and fungal organisms. mBD-3 mRNA expression was assayed by polymerase chain reaction (PCR) using cDNA derived from a panel of tissues. Expression of mBD-3 was also evaluated in tissues obtained from mice 24 h after intraperitoneal infection with Escherichia coli using reverse transcriptase (RT)-PCR. Synthetic mBD-3 inhibited the growth of E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans at concentrations from 25 to 50 microg/mL. Constitutive expression of mBD-3 mRNA was not consistently found in any organ using RT-PCR. In an E. coli peritonitis model, expression of mBD-3 mRNA was upregulated only in the esophagus and tongue. We conclude that mBD-3 is an inducible peptide with limited tissue expression during E. coli peritonitis. Because it exhibits broad-spectrum antimicrobial activity, this peptide may serve as an innate defense against microbial invasion at specific mucosal surfaces in the mouse.
Burd
Randall S
RS
Robert Wood Johnson Medical School, Department of Surgery, New Brunswick, New Jersey 08903, USA.
Furrer
Jason L
JL
Sullivan
Janet
J
Smith
Arnold L
AL
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D018805:Sepsis / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000187:drug effects; D014018:Tissue Distribution; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; C422950:DEFB103A protein, human; D011994:Recombinant Proteins; D023083:beta-Defensins