[Lung injury and pulmonary vascular endothelial cell injury]

Pulmonary vascular endothelial cells are an important barrier that helps keep lung tissue intact. These cells are exposed to potentially injurious cells and to harmful mediators that are produced in or released into the blood. The endothelial cells may then be stimulated and injured. Stimulated and injured pulmonary vascular endothelial cells can themselves produce and release injury-promoting mediators. Using isolated perfused rat lungs and cultured human pulmonary endothelial cells, we assessed the effect of neutrophil-derived injurious mediators, leukotoxin, and neutrophil elastase on the pulmonary endothelium. Both mediators caused high-permeability pulmonary edema in the isolated lungs and caused dose-dependent and time-dependent damage in the cell cultures. Injury due to leukotoxin was suppressed in the presence of LNMMA or superoxide dismutase and injury due to neutrophil elastase was suppressed by neutrophil elastase inhibitors. These data indicate that these mediators cause lung injury via different mechanisms and that they may synergistically evoke clinical lung injury.