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A study was conducted to determine if recombinant human soluble thrombomodulin can stem the increase of rat pulmonary vascular permeability induced by endotoxin through protein C activation. Results show that recombinant human soluble thrombomodulin treated with monoclonal antibody F2H5 cannot inhibit endotoxin-induced coagulation. Results also indicate that endotoxin-induced intravascular coagulation is inhibited by recombinant human soluble thrombomodulin through thrombin binding.

Specific pathogen-free male Wistar rats treated with lipopolysaccharide (LPS) were analyzed to determine the efficiency of activated protein C (APC) in preventing LPS-induced pulmonary vascular injury. Analysis of rats exhibiting LPS-induced organ damage indicated the role of APC in reducing LPS-induced pulmonary vascular injury by inhibiting the synthesis of tumor necrosis factor. Furthermore, prophylactic administration of APC before LPS prevented endothelial cell damage by inhibiting cytokine production.

Thrombomodulin (TM) is an edothelial cell membrane glycoprotein that forms a complex with thrombin, which activates protein C (APC) in plasma. Since APC is known to participate in the inhibition of endotoxin (ET)-induced lung injury, it is suggested that TM may also have a similar function. Using a rat model of ET-induced acute pulmonary vascular injury, experiments showed that TM prevents ET-induced lung injury by inhibiting the activation of leukocytes by generating APC.

Thrombin fails to mediate the pulmonary vascular injury induced by lipopolysaccharide (LPS) administration, while activated leukocytes affect it. Intravenous antithrombin III (AT III) suppresses pulmonary leukocyte accumulation and increases pulmonary vascular permeability to LPS-induced (SUP 125)I-bovine serum albumin. Leukocytopenia suppresses this increased permeability. Interaction between AT III and heparin-like substances at the endothelial cell surface leads to prostacyclin release. Prostacyclin prevents LPS-induced pulmonary leukocyte accumulation and vascular injury.