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Published ahead of print on July 25, 2002, doi:10.1164/rccm.200203-207OC
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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 1282-1289, (2002)
© 2002 American Thoracic Society

Original Article

Role of Deformation-induced Lipid Trafficking in the Prevention of Plasma Membrane Stress Failure

Nicholas E. Vlahakis, Mark A. Schroeder, Richard E. Pagano and Rolf D. Hubmayr

Pulmonary and Critical Care Medicine Division, Mayo Clinic and Foundation, Rochester, Minnesota

Correspondence and requests for reprints should be addressed to Nicholas E. Vlahakis, M.D., Stabile 8-62, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: vlahakis.nicholas{at}mayo.edu

Cells experience plasma membrane stress failure when the matrix to which they adhere undergoes large deformations. In the lung, such a mechanism might explain mechanical ventilation–associated cell injury. We have previously shown that in alveolar epithelial cells, deformation induces lipid trafficking to the plasma membrane, thereby accommodating the required increase in the cell surface area. We now show that cell wounding is strain amplitude and rate dependent and that under conditions of impaired exocytosis strain-induced cell wounding is significantly increased. In addition, the susceptibility of cells to mechanical injury was not correlated with changes in cell stiffness. Using a dual-labeling technique, we differentiated between cell populations that were reversibly and irreversibly injured and showed that interventions that impair deformation-induced lipid trafficking also reduce the likelihood of plasma membrane resealing. Our findings suggest that cell plasticity and remodeling responses such as deformation-induced lipid trafficking are more important for cytoprotection from strain injury than are the innate mechanical properties of the cell. We also conclude that in deformation experiments, tests of cell membrane integrity cannot be interpreted as tests of cell viability because an intact plasma membrane after deformation does not mean that no injury had occurred.

Key Words: exocytosis • plasma membrane wounding • plasma membrane resealing • ventilator-induced lung injury




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Copyright © 2002 American Thoracic Society 		  CCM abstracts