Effect of cyclic stretch on wound healing of airway epithelial cells

Asthma and obstructive airway diseases can result in epithelial shedding, and endotracheal intubation for mechanical ventilation can also cause epithelial ceil loss Since cyclic distension of airways occurs during normal breathing and mechanical ventilation, we investigated the influence of cyclic stretch on the rate of epithelial wound healing. Airway epithelial cells derived from a human lung adenocarcinoma (Calu 3) were grown to confluence on flexible silastic membranes. A strip of cells was denuded across the diameter of the membrane by a thin metal spatula, and cells were subjected to cyclic stretch (20% max. strain) by applying an oscillating vacuum (Flcxercell Intl.). Average wound width was measured using video microscopy after 24 and 4X hr. When cells were stretched at 10cycles/min(cpm), the wound width in the periphery of the well was 37 + 4% of the original wound compared with control cells which had closed to 35 ± 3% (n=12) In the center of the well where minimal strain occurs, the wounds had closed to 40 ± 6% compared with controls which had closed to 28 + 4% (n=6). Cells stretched at 30 cpm healed more slowly than control cells or cells stretched at 10 cpm. After 48 hr of stretch at 30 cpm, there was a significant difference in the percentage of the original wound width at the periphery (35 + 3%, p<0.05, n=12) compared with the controls (17 ±4%). In the middle of the wells, the wound width at 4X hr was also significantly larger than controls (47 + 4%, stretched, 25 + 4%, controls; n-6). These results show that epithelial wound healing is affected by cyclic stretch in a frequencydependent manner. Also, wounds healed more slowly in the middle of the stretched wells where strain was minimal. This may suggest the presence of a secreted factor which inhibits proliferation or migration.