Role of platelets in maintenance of pulmonary vascular permeability to protein

Abstract

We examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Qlym). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (Pla). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. Platelet count decreased from 460,000 +/- 77,000 to 16,000 +/- 4,000 platelets/microliters, without significant changes in the leukocyte count and hematocrit. Studies were made in three groups: 1) control sheep having a normal platelet count; 2) thrombocytopenic sheep; and 3) PRP-infused thrombocytopenic sheep. Elevation in Pla in control sheep increased pulmonary transvascular protein clearance (CL) to 12.1 +/- 2.1 ml/h, whereas the same Pla elevation in thrombocytopenia increased CL to 24.1 +/- 4.0 ml/h, indicating an increase in pulmonary vascular permeability to protein in thrombocytopenic animals. Infusion of PRP restored normal permeability, since it prevented the increase in CL. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelial permeability of 125I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 X 10(7) or 5 X 10(7) platelets were added onto endothelial monolayers. However, addition of 5 X 10(6) platelets or 5 X 10(7) red blood cells did not reduce endothelial monolayer albumin permeability.(ABSTRACT TRUNCATED AT 250 WORDS)