title: Inhibition of endotoxin effects on cultured human middle ear epithelium by bactericidal permeability-increasing protein.
abstract: OBJECTIVE
  Endotoxin can induce morphologic changes to middle ear epithelium, which can disturb the mucociliary clearance system (MCS) and lead to otitis media with effusion (OME). The bactericidal/permeability-increasing (BPI) protein is a major component of neutrophil granules and binds with high affinity to endotoxin. In this study, the capacity to inhibit the effects of endotoxin by rBPI21, a recombinant amino-terminal analog derived from BPI, was investigated on cultured human middle ear epithelium using light microscopy and scanning- and transmission electron microscopy.
  
  
  METHODS
  Human middle ear epithelium was air-exposed cultured on a collagenous underlayer with different additions of endotoxin and rBPI21 to the culture medium. The tissue specimens were inspected after 4 weeks for the number of ciliated and secretory cells, thickness of the mucosal layer, and cell size.
  
  
  RESULTS
  The morphologic changes induced by endotoxin were increased thickness of the mucosal layer and increased number of secretory cells. These changes were significantly diminished or even absent when endotoxin was added with rBPI21 to the culture medium.
  
  
  CONCLUSIONS
  rBPI21 can inhibit morphologic changes in the middle ear epithelium due to endotoxin. Hence, the authors believe that rBPI21 can be a new therapeutic agent in the treatment of OME.
authors.affiliation: Department of Otorhinolaryngology, Leiden University Medical Center, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Nell
authors.forename: B M
authors.initials: BM
authors.lastname: Albers-Op 't Hof
authors.forename: H K
authors.initials: HK
authors.lastname: Koerten
authors.forename: J J
authors.initials: JJ
authors.lastname: Grote
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002478:Cells, Cultured; D004432:Ear, Middle / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D004731:Endotoxins / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006193:Haemophilus influenzae / Q000378:metabolism*; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects; D009092:Mucous Membrane / Q000648:ultrastructure; D012486:Salmonella typhimurium / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins