Perfluorocarbon protects lung epithelial cells from neutrophil-mediated injury in an in vitro model of liquid ventilation therapy.
Liquid ventilation with perfluorocarbon has been effective in improving gas exchange and pulmonary function in the setting of acute respiratory failure. How improvement is brought about remains unknown. In the present study, we examined perfluorocarbon for effects on neutrophil function and for effects on neutrophil-epithelial cell interactions that could underlie its in vivo activity. Exposure of neutrophils in vitro to perfluorocarbon followed by washing did not interfere with their ability to generate oxidants or release proteolytic enzymes upon subsequent stimulation. Likewise, such treatment did not interfere with subsequent adhesion of the neutrophils to monolayers of epithelial cells or with neutrophil-induced injury to these cells. In contrast, when perfluorocarbon was added to neutrophils and epithelial cells together and the neutrophils then stimulated, it reduced their adhesive interaction with the target cells and concomitantly reduced target cell injury. In companion studies, cells were obtained by bronchial lavage of perfluorocarbon-treated patients with acute respiratory distress syndrome (ARDS) and analyzed for oxidant production. Oxidant-generating capacity by the cells obtained from the bronchial lavage fluid was similar to that of peripheral blood neutrophils. These data are consistent with the suggestion that perfluorocarbon protects cells in vitro from neutrophil-mediated injury, at least in part, by acting as a mechanical barrier. These findings are consistent with a potential mechanism of action in vivo.
Varani
J
J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Hirschl
R B
RB
Dame
M
M
Johnson
K
K
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D010450:Endopeptidases / Q000097:blood / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000293:injuries; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D012121:Respiration, Artificial / Q000379:methods*; D013481:Superoxides / Q000097:blood / Q000378:metabolism
D005466:Fluorocarbons; D013481:Superoxides; D006861:Hydrogen Peroxide; D010450:Endopeptidases