title: KL4-surfactant (Lucinactant) protects human airway epithelium from hyperoxia.
abstract: Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air-liquid interface were treated apically with 140 microL of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O(2)/5% CO(2) for 24 or 72 h. Transepithelial resistance (TER; p < 0.001) and cell viability (p < 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant (p < 0.001). Surfactant treated groups secreted less IL-8 than saline (p < 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant (p < 0.001). Matrix metalloproteinase 7, expressed by saline and Beractant treated cells at 24 h, was attenuated by 72 h by Beractant (p < 0.001), but was never detected in Lucinactant cells. Histology indicated less injury with Lucinactant relative to Beractant and saline. These data suggest that Lucinactant was protective compared with Beractant and control.
authors.affiliation: Nemours Research Lung Center, Alfred I duPont Hospital for Children, AR-282, Wilmington, DE 19803, USA. yzhu@nemours.org
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Miller
authors.forename: Aaron
authors.initials: A
authors.lastname: Chidekel
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Shaffer
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001688:Biological Products / Q000627:therapeutic use; D002478:Cells, Cultured; D006801:Humans; D018496:Hyperoxia / Q000150:complications / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011014:Pneumonia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; C097558:KL4 surfactant; D010455:Peptides; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; C072197:beractant