title: Erythromycin increases bactericidal activity of surface liquid in human airway epithelial cells.
abstract: Macrolide antibiotics have clinical benefits in patients with diffuse panbronchiolitis and in patients with cystic fibrosis. Although many mechanisms have been proposed, the precise mechanisms are still uncertain. We examined the effects of erythromycin on bactericidal activity of airway surface liquid secreted by cultured human tracheal epithelial cells. Airway surface liquid was collected by washing the surface of human tracheal epithelial cells with a sodium solution (40 meq/l). Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were incubated with airway surface liquid, and the number of surviving bacteria was examined. The number of bacteria in airway surface liquid from the cells cultured in medium alone was significantly lower than that in the sodium solution. Furthermore, the number of bacteria in airway surface liquid from the cells treated with erythromycin was significantly lower than that in airway surface liquid from the cells treated with solvent alone. The production of mRNA and protein of human beta-defensin-1 and human beta-defensin-2 was significantly increased by erythromycin. Bactericidal activity of airway surface liquid was observed at low concentrations (40 meq/l) of sodium but not at higher concentrations (> or =80 meq/l). Airway surface liquid did not contain significant amounts of antibiotics supplemented in the culture medium. Erythromycin at the levels in airway surface liquid and in culture medium did not inhibit bacterial growth. These results suggest that erythromycin may increase bactericidal activity of airway surface liquid in human airway epithelial cells through human beta-defensins production and reduce susceptibility of the airway to bacterial infection.
authors.affiliation: Dept. of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Jia
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
authors.forename: Hidetada
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004917:Erythromycin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D016106:Methicillin Resistance; D009113:Muramidase / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy; D014132:Trachea / Q000166:cytology; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins; D004917:Erythromycin; D012964:Sodium; D009113:Muramidase; D007781:Lactoferrin