Mechanisms of thrombin-induced lung vascular injury and edema.

We have examined the mechanisms of lung vascular injury and pulmonary edema secondary to intravascular coagulation. Alpha-thrombin was infused intravenously to induce pulmonary intravascular coagulation. The results indicate that fibrin and neutrophils are essential requirements for lung vascular injury and pulmonary edema formation. The findings point to a fibrin-neutrophil interaction in inducing neutrophil adherence. Thrombin also has direct effects on endothelial permeability and can contribute to neutrophil sequestration in the lung by increasing endothelial adhesivity. Complement activation can explain only a part of the response. Lipid-derived mediators (e.g., LTB4 and mono HETEs) may be particularly important in the pathophysiology of lung vascular injury and pulmonary edema.