TY - JOUR
T1 - Identification and Characterization of a Mucosal Antimicrobial Peptide Expressed by the Chinchilla (Chinchilla lanigera) Airway
AU - Harris, Randall H.
AU - Wilk, Dennis
AU - Bevins, Charles L
AU - Munson, Robert S.
AU - Bakaletz, Lauren O.
PY - 2004/5/7
Y1 - 2004/5/7
N2 - 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 13-defensin 3, designated chinchilla 13-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.
AB - 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 13-defensin 3, designated chinchilla 13-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.
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U2 - 10.1074/jbc.M400499200
DO - 10.1074/jbc.M400499200
M3 - Article
C2 - 14996845
AN - SCOPUS:2442439910
VL - 279
SP - 20250
EP - 20256
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -