Pulmonary neutrophil kinetics after thrombin-induced intravascular coagulation

Abstract

Previous studies have indicated that neutrophils are required for the development of increased lung vascular permeability after thrombin-induced pulmonary microembolization. In this study, we examined neutrophil kinetics and uptake in the sheep lung before and after lung vascular injury. Sheep neutrophils were isolated by a Percoll-gradient method and labeled with indium-111 oxine. A maximum lung activity of 40% of the injected indium-111 neutrophil activity was attained 8-12 min after the injection. The calculated half-lives of both circulating and pulmonary neutrophils were 700 min. The rate of washout of labeled neutrophils from the lungs was the same as the loss of the peripheral blood activity, indicating removal of neutrophils from the lung and blood by a common pathway (e.g., liver and spleen). Intravenous infusion of alpha-thrombin resulted in an immediate uptake of neutrophils of 14% above the base-line activity. The increased uptake was associated with an immediate decrease in the blood activity, indicating sequestration of the neutrophils in the pulmonary circulation. The neutrophil uptake after alpha-thrombin was transient, reaching a maximum 15 min after infusion. Neutrophil uptake did not occur with alpha-thrombin (which lacks the fibrinogen recognition site), suggesting that the uptake was secondary to intravascular coagulation. An increase in the pulmonary blood volume cannot explain the increased neutrophil sequestration because pulmonary blood volume determined by [99mTc]pertechnetate-labeled erythrocytes did not increase after the alpha-thrombin infusion. Therefore, alpha-thrombin results in a transient neutrophil sequestration in the lung, and the response is secondary to the intravascular coagulation induced by the alpha-thrombin.