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Stretch increases alveolar epithelial permeability to uncharged micromolecules
Kenneth J Cavanaugh1, Taylor S Cohen, Susan S Margulies
1Department of Bioengineering, 3320 Smith Walk, University of Pennsylvania, Philadelphia, 19104-6392, USA.
American Journal of Physiology. Cell Physiology
|November 12, 2005
Summary
High lung inflation (37% surface area change) significantly increases alveolar epithelial permeability to small molecules. This stretch-induced barrier failure is partially mediated by intracellular calcium and F-actin dynamics.
Area of Science:
- Pulmonary Physiology
- Cell Biology
- Biophysics
Background:
- The alveolar epithelial barrier is crucial for lung function.
- Understanding how mechanical forces like stretch affect barrier integrity is vital for treating lung injury.
Purpose of the Study:
- To identify the critical stretch threshold for alveolar epithelial barrier failure.
- To investigate the role of intracellular signaling pathways in stretch-induced permeability changes.
Main Methods:
- Cultured alveolar epithelial cells were subjected to cyclic biaxial stretch (12%, 25%, 37% DeltaSA).
- Transepithelial permeability to uncharged tracers (1.5-5.5 A radius) was measured.
- Inhibitors of protein kinase C, tyrosine kinase, intracellular calcium chelators, and F-actin stabilizers were used.
Main Results:
- A 37% DeltaSA significantly increased transepithelial permeability, particularly for larger tracers.
- Increased permeability correlated with increased pore radii in a pore population model.
- Inhibition of intracellular calcium and F-actin partially reduced stretch-induced permeability.
Conclusions:
- Large-magnitude stretch (37% DeltaSA) compromises alveolar epithelial barrier integrity in vitro.
- Stretch-induced permeability is partially mediated by intracellular calcium and F-actin.
- Findings are supported by whole lung data showing increased permeability at high inflation volumes.