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1 Department of Physiology, College of Medicine, and School of Biomedical Engineering, University of Tennessee Health Science Center, Memphis, Tennessee 38163; 2 Department of Medicine, Feinberg School of Medicine, Northwestern University, and Veterans Affairs Chicago Health Care System-Lakeside Division, Chicago, Illinois 60611; 3 Department of Surgery, University of Toronto, and Thoracic Surgery Research Laboratory, University Health Network Toronto General Hospital, Toronto, Ontario, Canada M5G 2C4; and 4 Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115
Mechanical forces affect both the function and phenotype of cells in the lung. In this symposium, recent studies were presented that examined several aspects of biomechanics in lung cells and their relationship to disease. Wound healing and recovery from injury in the airways involve epithelial cell spreading and migration on a substrate that undergoes cyclic mechanical deformation; enhanced green fluorescent protein-actin was used in a stable cell line to examine cytoskeletal changes in airway epithelial cells during wound healing. Eosinophils migrate into the airways during asthmatic attacks and can also be exposed to cyclic mechanical deformation; cyclic mechanical stretch caused a decrease in leukotriene C4 synthesis that may be dependent on mechanotransduction mechanisms involving the production of reactive oxygen species. Recent studies have suggested that proinflammatory cytokines are increased in ventilator-induced lung injury and may be elevated by overdistention of the lung tissue; microarray analysis of human lung epithelial cells demonstrated that cyclic mechanical stretch alone profoundly affects gene expression. Finally, airway hyperresponsiveness is a basic feature of asthma, but the relationship between airway hyperresponsiveness and changes in airway smooth muscle (ASM) function remain unclear. New analysis of the behavior of the ASM cytoskeleton (CSK) suggests, however, that the CSK may behave as a glassy material and that glassy behavior may account for the extensive ASM plasticity and remodeling that contribute to airway hyperresponsiveness. Together, the presentations at this symposium demonstrated the remarkable and varied roles that mechanical forces may play in both normal lung physiology as well as pathophysiology.
actin remodeling; 5-lipoxygenase; inflammatory cytokines; mechanical properties
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