Murine beta-defensin-3 Is an Inducible Peptide With Limited Tissue Expression and Broad-Spectrum Antimicrobial Activity

Shock. 2002 Nov;18(5):461-4. doi: 10.1097/00024382-200211000-00013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents
  • Anti-Infective Agents / pharmacology
  • Candida albicans / drug effects
  • Escherichia coli / drug effects
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / immunology
  • Female
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Pseudomonas aeruginosa / drug effects
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Sepsis / genetics
  • Sepsis / immunology
  • Staphylococcus aureus / drug effects
  • Tissue Distribution
  • beta-Defensins / biosynthesis*
  • beta-Defensins / genetics
  • beta-Defensins / pharmacology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • DEFB103A protein, human
  • Recombinant Proteins
  • beta-Defensins