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J. Biol. Chem., Vol. 279, Issue 19, 20250-20256, May 7, 2004

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Identification and Characterization of a Mucosal Antimicrobial Peptide Expressed by the Chinchilla (Chinchilla lanigera) Airway^*

Randall H. Harris, Dennis Wilk, Charles L. Bevins, Robert S. Munson, Jr., and Lauren O. Bakaletz¶

From the Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43205 and the Department of Immunology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

Cationic antimicrobial peptides (APs) are produced at mucosal surfaces and play a key role as a first line of defense against infection. To understand how APs might impact disease progression in otitis media (OM), our goal was to identify and characterize APs expressed by the epithelium lining the uppermost airway of the chinchilla, the established rodent host for the study of the bacterial-viral pathogenesis in OM. Using a molecular approach, we cloned a cDNA encoding a homolog of human -defensin 3, designated chinchilla -defensin-1 (cBD-1), and found by Northern analysis expression of the corresponding mRNA in nasopharyngeal and tongue mucosae as well as skin. By reverse transcription-PCR, cBD-1 mRNA was also detected in RNA isolated from trachea, lung, and Eustachian tube tissues. The predicted mature form of cBD-1, expressed as a recombinant peptide in Escherichia coli, demonstrated bactericidal activity against the three primary opportunistic pathogens of OM as well as Candida albicans. Continued study of this and other APs will allow us to determine their role in bacterial colonization of the upper airway as well as how viruses might contribute to the pathogenesis of OM by modulating AP expression.

Received for publication, January 16, 2004

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY128668.

^* This work was supported by NIDCD, National Institutes of Health (NIH), Grant R01-DC05847 (to L. O. B.). The DNA Sequencing Core at Columbus Children's Research Institute was supported in part by NIH Grant HD34615. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Dept. of Pediatrics, The Ohio State University, College of Medicine and Public Health, Columbus Children's Research Institute, Center for Microbial Pathogenesis, 700 Children's Dr., Rm. W591, Columbus, OH 43205-2696. Tel.: 614-722-2915; Fax: 614-722-2007; E-mail: BakaletL{at}pediatrics.ohio-state.edu.

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