Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia

摘要: Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both inflammation in sepsis. In this study, we used genetic pharmacologic approaches analyze the role tissue factor protease-activated receptors mouse endotoxemia model. We mice expressing low levels procoagulant molecule, (TF), effects TF deficiency either all tissues or selectively hematopoietic cells. Low had reduced coagulation, inflammation, mortality compared control mice. Similarly, expression by cells lipopolysaccharide (LPS)-induced mortality. Inhibition down-stream protease, thrombin, fibrin deposition prolonged survival without affecting inflammation. Deficiency protease activated receptor-1 (PAR-1) receptor-2 (PAR-2) alone did not affect survival. However, combination thrombin inhibition PAR-2 These data demonstrate that are major pathologic site during suggest multiple mediate crosstalk between