Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 290, Issue 4, Pages C1179-C1188Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00355.2004
Keywords
ventilator-induced lung injury; acute lung injury; barrier properties
Categories
Funding
- NHLBI NIH HHS [R01 HL057204-03, R01 HL-57204, R01 HL057204] Funding Source: Medline
Ask authors/readers for more resources
We measured stretch-induced changes in transepithelial permeability in vitro to uncharged tracers 1.5-5.5 angstrom in radius to identify a critical stretch threshold associated with failure of the alveolar epithelial transport barrier. Cultured alveolar epithelial cells were subjected to a uniform cyclic (0.25 Hz) biaxial 12, 25, or 37% change in surface area (Delta SA) for 1 h. Additional cells served as unstretched controls. Only 37% Delta SA (100% total lung capacity) produced a significant increase in transepithelial tracer permeability, with the largest increases for bigger tracers. Using the permeability data, we modeled the epithelial permeability in each group as a population of small pores punctuated by occasional large pores. After 37% Delta SA, increases in paracellular transport were correlated with increases in the radii of both pore populations. Inhibition of protein kinase C and tyrosine kinase activity during stretch did not affect the permeability of stretched cells. In contrast, chelating intracellular calcium and/or stabilizing F-actin during 37% Delta SA stretch reduced but did not eliminate the stretch-induced increase in paracellular permeability. These results provide the first in vitro evidence that large magnitudes of stretch increase paracellular transport of micromolecules across the alveolar epithelium, partially mediated by intracellular signaling pathways. Our monolayer data are supported by whole lung permeability results, which also show an increase in alveolar permeability at high inflation volumes (20 ml/ kg) at the same rate for both healthy and septic lungs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available