title: Correlative ultrastructural investigations of airway epithelium following experimental exposure to defined air pollutants and lifestyle exposure to tobacco smoke.
abstract: BACKGROUND
  Investigations of cell/molecular level effects of in vivo exposure of airway mucosa of experimental animals to common irritant gases have demonstrated structural and physiological changes reflective of breaches in epithelial barrier function, presence of inflammatory cell infiltrate and compromised ciliary function. These experimental animal studies provided useful perspectives of plausible, but more subtle pathologic outcomes having relevance to lifestyle exposure to gaseous environmental irritants including tobacco smoke.
  
  
  METHODS
  Freeze-fracture technology was applied to ultrastructural examination of large airway epithelium, with appropriate controls, from guinea pigs exposed to ozone and of nasal mucosa of human subjects exposed to ozone or sulfur dioxide, and nasal mucosa of active smokers.
  
  
  RESULTS
  We documented substantive membrane structural changes to tight junctional complexes and cilia as well as an infiltrate of neutrophils into the surface mucosal layer in exposed animals. These patterns also were evident but not as pervasive among human subjects acutely exposed experimentally to irritant gases and those chronically exposed by their lifestyle to tobacco smoke.
  
  
  CONCLUSIONS
  Our intent was to characterize respiratory tract mucosal membrane disorganization associated with high level acute irritant exposures in an experimental animal model and to evaluate evidence of similar but perhaps more subtle pathologic change associated with lower level experimental or lifestyle exposures. Our studies demonstrate continuity, albeit subtle, of pathologic change from high dosage experimental animal exposure to low dosage human exposures.
  
  
  CONCLUSIONS
  This study represents the first report of ultrastructural airway epithelial membrane anomalies associated with lifestyle exposure to tobacco smoke irritants.
authors: Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jcarson@med.unc.edu
authors: Johnny L
authors: JL
authors: Carson
authors: Luisa E
authors: LE
authors: Brighton
authors: Albert M
authors: AM
authors: Collier
authors: Philip A
authors: PA
authors: Bromberg
mesh_terms: D000818:Animals; D001706:Biopsy; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003367:Cotinine / Q000652:urine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005614:Freeze Fracturing / Q000379:methods; D006168:Guinea Pigs; D006801:Humans; D008019:Life Style; D008297:Male; D046529:Microscopy, Electron, Transmission; D009297:Nasal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000473:pathology; D013458:Sulfur Dioxide / Q000633:toxicity*; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure; D014028:Tobacco Smoke Pollution / Q000009:adverse effects* / Q000032:analysis; D014132:Trachea / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D010083:Oxidants, Photochemical; D014028:Tobacco Smoke Pollution; D013458:Sulfur Dioxide; D010126:Ozone; D003367:Cotinine