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The Journal of Immunology, 2002, 169: 2516-2523.
Copyright © 2002 by The American Association of Immunologists

Identification of Multiple Novel Epididymis-Specific {beta}-Defensin Isoforms in Humans and Mice1

Yasuhiro Yamaguchi*,{dagger}, Takahide Nagase{dagger}, Ryosuke Makita*, Shigetomo Fukuhara*, Tetsuji Tomita{dagger}, Takashi Tominaga{ddagger}, Hiroki Kurihara2,* and Yasuyoshi Ouchi{dagger}

* Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; and {dagger} Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, and {ddagger} Department of Urology, Mitsui Memorial Hospital, Tokyo, Japan

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 HE2{beta}1, 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.




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