Granulocytes mediate the increase in pulmonary vascular permeability after thrombin embolism

We examined the effect of pulmonary embolization with microthrombi on the lung vascular permeability to proteins and the role of platelets and granulocytes as putative cellular factors in mediating the alterations in permeability. Anesthetized artificially ventilated sheep were prepared with lung lymph fistulas. Pulmonary embolization was induced using thrombin. Pulmonary vascular resistance (PVR) was increased approximately threefold from baseline. Pulmonary lymph flow (Qlym) increased 2 h after thrombin, but the lymph-to-plasma protein ratio (L/P) did not change significantly from base line. Raising the pulmonary capillary pressure (Pc) by inflating a left atrial balloon produced a large increase in Qlym but no change in L/P, indicating a permeability-increasing effect of thrombin. Reduction of platelet count with antiplatelet serum before thrombin also produced an increase in Qlym without a change in L/P. Raising Pc in this group resulted in changes comparable with those in the control group, i.e., increased Qlym without a change in L/P. In contrast to both control and platelet-depleted groups, reduction of the granulocyte count with hydroxyurea did not affect Qlym or L/P after thrombin. Raising Pc in this group increased Qlym but decreased L/P, indicating normal capillary sieving of proteins. Therefore embolization of pulmonary vessels with microthrombi increases pulmonary vascular permeability, and the increase is mediated by granulocytes.