Role of Stretch on Tight Junction Structure in Alveolar Epithelial Cells
| Autor: | Kenneth J. Cavanaugh, Jane Oswari, Susan S. Margulies |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Blotting Western Clinical Biochemistry Respiratory Mucosa Biology Occludin Tight Junctions Rats Sprague-Dawley Adenosine Triphosphate Tidal Volume medicine Animals Glycolysis Cytoskeleton Molecular Biology Cells Cultured Actin Tight junction Membrane Proteins Cell Biology Phosphoproteins Actins Epithelium Rats Cell biology Pulmonary Alveoli Blot medicine.anatomical_structure Zonula Occludens-1 Protein Stress Mechanical Intracellular |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 25:584-591 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Previous studies have demonstrated that high tidal volumes can cause interstitial and alveolar edema, with degradation of pulmonary epithelial barrier integrity. Separate studies have shown that F-actin disruption and decreased intracellular ATP (ATP(i)) levels in the nonpulmonary epithelium can increase tight junction (TJ) permeability. We hypothesized that large epithelial stretch perturbs ATP(i) and actin architecture, each of which adversely affects TJ structure, and thus increases TJ permeability. Primary alveolar epithelial cells were subjected to a uniform 25% or 37% change in surface area (DeltaSA), cyclic biaxial stretch (15 cycles/min) for 1 h, or treated with either glycolytic metabolic inhibitors or cytoskeletal disrupting agents. Unstretched, untreated cells served as controls. Changes in the TJ proteins occludin and ZO-1 were determined by immunocytochemical evaluation. A stretch amplitude of 25% DeltaSA did not produce any significant cytologic changes compared with controls, but an amplitude of 37% DeltaSA stretch resulted in significant decreases in the intensity of the peripheral occludin band, the degree of cell-cell attachment (CCA), and total cellular occludin content. ATP depletion significantly diminished the occludin band intensity and decreased CCA. Actin disruption did not affect TJ protein band intensities (although the occludin distribution became punctate) but altered CCA. Untreated cells stretched cyclically at 25% or 50% DeltaSA for 1 h had significantly decreased ATP(i) compared with unstretched controls. These results suggest that stretch-induced ATP(i) reduction and actin perturbation disrupt TJ structure and CCA, which may lead to the alveolar flooding associated with high tidal volumes. |
| Databáze: | OpenAIRE |
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