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An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance
Published on: December 3, 2020
PEEP-induced changes in epithelial permeability in inbred mouse strains
John M Bishai1, Wayne Mitzner, Clarke G Tankersley
1Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. jbishai@jhsph.edu
Respiratory Physiology & Neurobiology
|December 1, 2006
Summary
Susceptible C57Bl/6J mice exhibit a greater change in lung epithelial barrier function than resistant C3H/HeJ mice when lung volume is increased. This suggests fundamental differences in lung architecture between strains may influence irritant susceptibility.
Area of Science:
- Pulmonary toxicology
- Comparative immunology
- Respiratory physiology
Background:
- Inbred mouse strains exhibit varying susceptibility to inhaled environmental irritants like ozone.
- C57Bl/6J mice are susceptible, while C3H/HeJ mice are resistant, but lavaged protein measures both endothelial and epithelial barrier integrity.
- Basal differences in the lung epithelial barrier between strains remain unclear.
Purpose of the Study:
- To investigate basal differences in lung epithelial barrier function between C57Bl/6J and C3H/HeJ mice.
- To assess epithelial barrier permeability under varying lung volumes and positive end-expiratory pressure (PEEP).
Main Methods:
- Measured soluble tracer ((99m)technetium-diethylenetriamine pentaacetic acid, (99m)Tc-DTPA) clearance from the lung in anesthetized mice.
- Utilized spontaneous breathing and mechanical ventilation with increased lung volume and PEEP (1, 6, or 10 cmH2O).
Main Results:
- Both mouse strains demonstrated more rapid (99m)Tc-DTPA clearance during ventilation with 10 cmH2O PEEP compared to lower pressures (p<0.001).
- A significant difference in clearance rates was observed between strains at 10 cmH2O PEEP: C57Bl/6J mice (mean half time=19±4 min) vs. C3H/HeJ mice (mean half time=34±3 min) (p<0.001).
Conclusions:
- When lung volume is increased, the susceptible C57Bl/6J strain exhibits a greater change in epithelial barrier permeability than the resistant C3H/HeJ strain.
- These findings suggest that inherent differences in lung architecture may underlie the differential susceptibility of mouse strains to inhaled irritants.
