Deformation-induced lipid trafficking in alveolar epithelial cells.
Mechanical ventilation with a high tidal volume results in lung injury that is characterized by blebbing and breaks both between and through alveolar epithelial cells. We developed an in vitro model to simulate ventilator-induced deformation of the alveolar basement membrane and to investigate, in a direct manner, epithelial cell responses to deforming forces. Taking advantage of the novel fluorescent properties of BODIPY lipids and the fluorescent dye FM1-43, we have shown that mechanical deformation of alveolar epithelial cells results in lipid transport to the plasma membrane. Deformation-induced lipid trafficking (DILT) was a vesicular process, rapid in onset, and was associated with a large increase in cell surface area. DILT could be demonstrated in all cells; however, only a small percentage of cells developed plasma membrane breaks that were reversible and nonlethal. Therefore, DILT was not only involved in site-directed wound repair but might also have served as a cytoprotective mechanism against plasma membrane stress failure. This study suggests that DILT is a regulatory mechanism for membrane trafficking in alveolar epithelia and provides a novel biological framework within which to consider alveolar deformation injury and repair.
Vlahakis
N E
NE
Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. vlahakis@nicholas@mayo.edu
Schroeder
M A
MA
Pagano
R E
RE
Hubmayr
R D
RD
D001896:Boron Compounds; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003911:Dextrans / Q000493:pharmacokinetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D050356:Lipid Metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D015203:Reproducibility of Results; D013314:Stress, Mechanical
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D003911:Dextrans; C073804:FM1 43; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate