title: A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media.
abstract: Cationic antimicrobial peptides (AMPs), a component of the innate immune system, play a major role in defense of mucosal surfaces against a wide spectrum of microorganisms such as viral and bacterial co-pathogens of the polymicrobial disease otitis media (OM). To further understand the role of AMPs in OM, we cloned a cDNA encoding a cathelicidin homolog (cCRAMP) from upper respiratory tract (URT) mucosae of the chinchilla, the predominant host used to model experimental OM. Recombinant cCRAMP exhibited alpha-helical secondary structure and killed the three main bacterial pathogens of OM. In situ hybridization showed cCRAMP mRNA production in epithelium of the chinchilla Eustachian tube and RT-PCR was used to amplify cCRAMP mRNA from several other tissues of the chinchilla URT. Quantitative RT-PCR analysis of chinchilla middle ear epithelial cells (CMEEs) incubated with either viral (influenza A virus, adenovirus, or RSV) or bacterial (nontypeable H. influenzae, M. catarrhalis, or S. pneumoniae) pathogens associated with OM demonstrated distinct microbe-specific patterns of altered expression. Collectively, these data showed that viruses and bacteria modulate AMP messages in the URT, which likely contributes to the disease course of OM.
authors.affiliation: Columbus Children's Research Institute, Center for Microbial Pathogenesis and The Ohio State University College of Medicine & Public Health, 700 Children's Drive, Rm. W591, Columbus, OH 43205, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: McGillivary
authors.forename: William C
authors.initials: WC
authors.lastname: Ray
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.forename: Robert S
authors.initials: RS
authors.lastname: Munson
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D001419:Bacteria; D002682:Chinchilla / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000378:metabolism; D004432:Ear, Middle / Q000382:microbiology / Q000821:virology; D005064:Eustachian Tube / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010033:Otitis Media / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D012137:Respiratory System / Q000378:metabolism*; D014780:Viruses; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054804:Cathelicidins