title: Frequency and peak stretch magnitude affect alveolar epithelial permeability.
abstract: The present study measured stretch-induced changes in transepithelial permeability to uncharged tracers (1.5-5.5 A) using cultured monolayers of alveolar epithelial type-I like cells. Cultured alveolar epithelial cells were subjected to uniform cyclic (0, 0.25 and 1.0 Hz) biaxial stretch from 0% to 12, 25 or 37% change in surface area (DeltaSA) for 1 h. Significant changes in permeability of cell monolayers were observed when stretched from 0% to 37% DeltaSA at all frequencies, and from 0% to 25% DeltaSA only at high frequency (1 Hz), but not at all when stretched from 0% to 12% DeltaSA compared with unstretched controls. At stretch oscillation amplitudes of 25 and 37% DeltaSA, imposed at 1 Hz, tracer permeability increased compared with that at 0.25 Hz. Cells subjected to a single stretch cycle at 37% DeltaSA (0.25 Hz), to simulate a deep sigh, were not distinguishable from unstretched controls. Reducing stretch oscillation amplitude while maintaining a peak stretch of 37% DeltaSA (0.25 Hz) via the application of a simulated post-end-expiratory pressure did not protect barrier properties. In conclusion, peak stretch magnitude and stretch frequency were the primary determining factors for epithelial barrier dysfunction, as opposed to oscillation amplitude.
authors.affiliation: Dept of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Cohen
authors.forename: K J
authors.initials: KJ
authors.lastname: Cavanaugh
authors.forename: S S
authors.initials: SS
authors.lastname: Margulies
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry; D005541:Forced Expiratory Volume; D008297:Male; D008854:Microscopy, Electron; D008954:Models, Biological; D009991:Oscillometry; D010539:Permeability; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism
chemical_list: D005353:Fibronectins