MOUSE BETA-DEFENSIN-1 IS A SALT-SENSITIVE ANTIMICROBIAL PEPTIDE PRESENT IN EPITHELIA OF THE LUNG AND UROGENITAL TRACT

One component of host defense at mucosal surfaces appears to be epithe lium-derived peptides with antimicrobial activity called defensins. Hu man beta-defensin 1 (hBD-1) represents the first member of the beta-de fensin family isolated from humans and has been implicated in the path ogenesis of cystic fibrosis. We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse beta-de fensin 1 (mBD-1). The predicted amino acid sequence shows the hallmark features of other known epithelial beta-defensins, including the orde red array of six cysteine residues. Analysis of a genomic clone of mBD -1 revealed two exons separated by a 15-kb intron. By use of fluoresce nce in situ hybridization, the mBD-1 gene was localized at the proxima l portion of chromosome 8, the site where mouse a-defensins are found. Lysates from cells transfected with the mBD-1 cDNA showed antibacteri al activity against gram-positive and gram-negative bacteria. mBD-1 tr anscripts were found in kidney, liver, and female reproductive organ t issues. In the airways, mBD-1 is expressed diffusely throughout the ep ithelial cells of the large proximal airways with less expression in t he small distal airways and no expression in alveolar cells. The prese nt study demonstrates that a beta-defensin potentially homologous to h uman beta-defensin 1 is present in the respiratory system and other mu cosal surfaces in mice.