title: Staphylococcal alpha-toxin causes increased tracheal epithelial permeability.
abstract: Staphylococcus aureus is an important cause of pulmonary infections. The role of S. aureus alpha-toxin as a virulence factor is unclear. We hypothesized that airway epithelium is a target of S. aureus alpha-toxin and that exposure of airway epithelium to alpha-toxin results in damage to the airway epithelium. To examine the hypothesis that alpha-toxin is capable of independently producing airway epithelium damage as measured by permeability and morphometry, an isolated whole mouse trachea test apparatus was developed. In vitro epithelial permeability (P) was calculated and digital micrographs were analyzed morphometrically. Purified S. aureus alpha-toxin produced a significant increase in tracheal epithelial P (P < 0.05). Morphometric analysis revealed the ratio of adherent tracheal epithelium attached to the basement membrane divided by the total length of the basement membrane decreased in a dose-dependent manner with 1 microg/ml alpha-toxin and 10 microg/ml alpha-toxin (P < 0.05). We developed a novel isolated whole mouse trachea test apparatus for the measurement of tracheal epithelium damage. Increased P and separation of the tracheal epithelium from the basement membrane occurred after S. aureus alpha-toxin exposure. We conclude that mammalian airway epithelium is a target of S. aureus alpha-toxin.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA. phill071@umn.edu
authors.forename: James R
authors.initials: JR
authors.lastname: Phillips
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Tripp
authors.forename: Warren E
authors.initials: WE
authors.lastname: Regelmann
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
authors.forename: O Douglas
authors.initials: OD
authors.lastname: Wangensteen
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003911:Dextrans / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005098:Exotoxins / Q000633:toxicity; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006460:Hemolysin Proteins / Q000633:toxicity*; D008297:Male; D051379:Mice; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014136:Tracheitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D001427:Bacterial Toxins; D003911:Dextrans; D005098:Exotoxins; D006460:Hemolysin Proteins; C015219:fluorescein isothiocyanate dextran; C021091:staphylococcal alpha-toxin; D016650:Fluorescein-5-isothiocyanate