Lipopolysaccharide induction of tissue factor expression in rabbits

Tissue factor (TF) is the major activator of the coagulation protease casca de and contributes to lethality in sepsis, Despite several studies analyzin g TF expression in animal models of endotoxemia, there remains debate about the cell types that are induced to express TF in different tissues. In thi s study, we performed a detailed analysis of the induction of TF mRNA and p rotein expression in two rabbit models of endotoxemia to better understand the cell types that may contribute to local fibrin deposition and dissemina ted intravascular coagulation. Northern blot analysis demonstrated that lip opolysaccharide (LPS) increased TF expression in the brain, lung, and kidne y. In situ hybridization showed that TF mRNA expression was increased in ce lls identified morphologically as epithelial cells in the lung and as astro cytes in the brain. In the kidney, In situ hybridization experiments and im munohistochemical analysis showed that TF mRNA and protein expression was i ncreased in renal glomeruli and induced in tubular epithelium. Dual stainin g for TF and vWF failed to demonstrate TF expression in endothelial cells i n LPS-treated animals. These results demonstrate that TF expression is indu ced in many different cell types in LPS treated rabbits, which may contribu te to local fibrin deposition and tissue injury during endotoxemia.