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Deformation-induced Lung Cell Injury Is Glucose Concentration and Cell Type Dependent

¹ Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota

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

In critically ill patients, the use of insulin to maintain normoglycemia is associated with a lower incidence of bacteremia and improved mortality and morbidity. The physiologic mechanism for this protection is unclear, but maintenance of "normal" cell metabolism and thus mechanoprotective cell functions might help preserve lung cell integrity and decrease the risk of ventilator-induced lung injury. Our aim was to determine the effect of glucose concentration on cell injury after mechanical deformation in lung cells. Rat type II (ATII) or A549 alveolar epithelial or primary human pulmonary endothelial cells were cultured in the presence of varying glucose concentrations for 24 hours and stretched by repetitively deforming the membrane for 2 minutes at a constant strain rate but varying strain amplitude. Cell injury and death was determined by labeling cells in the presence of 1% fluorescein isothiocyanate–dextran during stretch and propidium iodide after stretch. Deformation-induced cell injury was greater in all cells grown in nonphysiologic glucose concentrations. The cell injury index varied significantly across all cell types, the lowest being in the human alveolar epithelial A549 cells. Furthermore, the ratio of injured-and-dead cells to injured-and-repaired cells varied across cell type (the highest in rat ATII cells), but not glucose concentration. Pericellular glucose concentration is an important determinant of deformation-induced lung cell injury and death. The predisposition to injury is also lung cell type dependent. Based on our previous findings, these results suggest that protective lipid exocytosis to the plasma membrane is impaired by nonphysiologic pericellular glucose concentrations. We hypothesize this is through glucose-induced changes in cystoskeletal structure and function.

FOOTNOTES

Supported by Mayo Foundation and Annenberg Foundation Research Award.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form July 24, 2007; accepted in final form October 16, 2007)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ayo, D. S. Articles by Vlahakis, N. E. PubMed Articles by Ayo, D. S. Articles by Vlahakis, N. E.