EXPRESSION OF TISSUE FACTOR AND TISSUE FACTOR PATHWAY INHIBITOR IN RAT LUNGS WITH LIPOPOLYSACCHARIDE-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION

Disseminated intravascular coagulation (DIG) is a frequent complicatio n of endotoxin shock, and modulation of endothelial cell hemostatic pr operties has been proposed to play an important role in its onset. We examined the in vivo expression of tissue factor (TF) and TF pathway i nhibitor (TFPI) in rat lungs of a lipopolysaccharide (LPS)-induced DIC model. Light and electron microscopic studies showed that fibrin-rich thrombi were present in the pulmonary microvasculature 3 hours after intraperitoneal injection of LPS (7.5 mg/kg) and increased in number a t 6 hours. In an immunohistochemical study, an increase in number of m onocytes in the microvasculature was observed after LPS injection, and many of these cells (>90%) were positive for TF antigen. However, no TF expression in endothelial cells was detected. Pulmonary endothelial cells showed positive reaction for TFPI antigen before LPS injection, but TFPI-positive endothelial cells markedly decreased in number afte r LPS injection. mRNA expression of TF increased and that of TFPI decr eased in the lung tissue 3 and 6 hours after LPS injection. High value s of TF activity were detected in the lung tissue and plasma, whereas TFPI activities decreased after LPS injection. These results indicate that imbalance between TF and TFPI, overexpression of TF, and underexp ression of TFPI in the lung may contribute to thrombus formation in th is LPS-induced DIC model.