title: PEEP-induced changes in epithelial permeability in inbred mouse strains.
abstract: Inbred mouse strains have demonstrated a range of susceptibilities to inhaled environmental irritants. C57Bl/6J mice are highly susceptible while C3H/HeJ mice are resistant to ozone exposures, as assessed by lavaged protein. However, lavaged protein reflects a loss of both the endothelial and epithelial barrier. To determine whether basal differences exist in the epithelial barrier, we measured soluble tracer ((99m)technetium-diethylenetriamine pentaacetic acid, (99m)Tc-DTPA) clearance from the lung in spontaneously breathing, anesthetized mice and mice ventilated with increased lung volume with applied positive end-expiratory pressure (PEEP; 1, 6, or 10cmH(2)O). Both strains showed more rapid clearance during ventilation with 10cmH(2)O PEEP compared with other ventilation pressures (p<0.001). There was a substantial difference in clearance between the two strains during ventilation with 10cmH(2)O PEEP (mean half time for C57Bl/6J mice=19+/-4min versus 34+/-3min for C3H/HeJ mice; p<0.001). Thus, when lung volume is increased, the susceptible C57Bl/6J strain shows a greater change in epithelial barrier than the resistant C3H/HeJ strain. These results may reflect fundamental differences in lung architecture.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. jbishai@jhsph.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Bishai
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.forename: Clarke G
authors.initials: CG
authors.lastname: Tankersley
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wagner
mesh_terms: D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000502:physiology; D008176:Lung Volume Measurements; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009079:Mucociliary Clearance; D010539:Permeability; D011175:Positive-Pressure Respiration; D011506:Proteins / Q000378:metabolism; D019275:Radiopharmaceuticals; D012121:Respiration, Artificial; D020545:Respiratory Mucosa / Q000502:physiology*; D013045:Species Specificity; D016284:Technetium Tc 99m Pentetate
chemical_list: D011506:Proteins; D019275:Radiopharmaceuticals; D016284:Technetium Tc 99m Pentetate