Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice

• Published in: The Journal of immunology (1950) 2002-09, Vol.169 (5), p.2516-2523
• Main Authors: Yamaguchi, Yasuhiro, Nagase, Takahide, Makita, Ryosuke, Fukuhara, Shigetomo, Tomita, Tetsuji, Tominaga, Takashi, Kurihara, Hiroki, Ouchi, Yasuyoshi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antigens, Surface - chemistry; Antigens, Surface - genetics; Base Sequence; beta-Defensins - chemistry; beta-Defensins - genetics; beta-Defensins - pharmacology; Epididymis - chemistry; Epididymis - immunology; Escherichia coli - drug effects; Escherichia coli - growth & development; Glycopeptides - chemistry; Glycopeptides - genetics; Humans; Male; Mice; Mice, Inbred ICR; Molecular Sequence Data; Multigene Family - immunology; Organ Specificity - genetics; Organ Specificity - immunology; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - pharmacology; Recombinant Proteins; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.5.2516

Defensins comprise a family of cationic antimicrobial peptides that are characterized by the presence of six conserved cysteine residues. We identified two novel human beta-defensin (hBD) isoforms by mining the public human genomic sequences. The predicted peptides conserve the six-cysteine motif identical with hBD-4, termed hBD-5 and hBD-6. We also evaluated the characteristics of the mouse homologs of hBD-5, hBD-6, and HE2beta1, termed mouse beta-defensin (mBD)-12, mBD-11, and mouse EP2e (mEP2e). The mBD-12 synthetic peptide showed salt-dependent antimicrobial activity. We demonstrate the epididymis-specific expression pattern of hBD-5, hBD-6, mBD-11, mBD-12, and mEP2e. In situ hybridization revealed mBD-11, mBD-12, and mEP2e expression in the columnar epithelium of the caput epididymis, contrasting with the predominant expression of mBD-3 in the capsule or septum of the whole epididymis. In addition, the regional specificity of mBD-11, mBD-12, and mEP2e was somewhat overlapping, but not identical, in the caput epididymis, suggesting that specific regulation may work for each member of the beta-defensin family. Our findings indicated that multiple beta-defensin isoforms specifically and cooperatively contribute to the innate immunity of the urogenital system.