Tissue factor is expressed in the vascular adventitia, but may also be expressed in micro-particles which can be shed from leukocytes, endothelial cells, vascular smooth muscle cells and platelets[13]. In the normal setting TF is not in contact with circulating blood. When vessels are injured or http://www.selleckchem.com/products/Trichostatin-A.html when TF-expressing cells are stimulated by circulating pro-inflammatory cytokines or lipopolysaccharide (LPS), TF is exposed to the bloodstream. TF then binds and activates factor VII. Factor VII is a vitamin K-dependent trypsin-like serine protease, produced in the liver. It circulates in an inactive form, and requires the action of its allosteric regulator, TF, to convert it to the active enzyme (FVIIa). The TF-factor VII complex initiates coagulation by activating FX, eventually resulting in conversion of pro-thrombin to thrombin.

Thrombin cleaves fibrinogen, resulting in abundant fibrin production and the formation of a clot. The activity of TF is counterbalanced by circulating tissue factor pathway inhibitor (TFPI). In addition to its well-established role in coagulation, TF, and to a lesser extent FVII, have also been associated with various other physiological processes of gene transcription, apoptosis and cytoskeleton reformation, such as in inflammation, sepsis, metastasis, angiogenesis and atherosclerosis, where the TF-FVIIa complex acts as a signalling receptor[14-17]. The role of TF/FVIIa signalling in inflammatory conditions is confirmed by TF/FVIIa regulated expression of the pro-inflammatory cytokine interleukin (IL)-8 in keratinocytes[18], and a role in the regulation of both IL-6 and IL-8 expression in monocytes/macrophages[19].

Confirming the effect of FVIIa on expression of interleukins, recombinant FVIIa administered to healthy humans caused a three- to four-fold increase in plasma levels of IL-6 and IL-8[20]. A role of TF/FVIIa signalling in the regulation of inflammatory genes has been demonstrated in LPS-stimulated macrophages, where TF-FVIIa signalling activated genes coding for tumor necrosis factor-��, IL-6, and IL-8[21]. Recent clinical studies have suggested a potential role of coagulation variables, such as TF, TFPI and D-dimer, in predicting risk of developing organ failure and severe AP[22-24]. However, the evidence supporting their use as predictors of severity of AP is still weak, compared to C-reactive protein (CRP) and IL-6, which to date are the most well-documented laboratory parameters to predict severe AP[25-28].

The present study aimed to investigate plasma Drug_discovery levels of TF in the initial phase of predicted severe AP, and to assess the ability of this biochemical marker to predict severe AP. MATERIALS AND METHODS Consecutive patients admitted to Lund University Hospital with the clinical diagnosis of acute pancreatitis, were recruited prospectively between June 2002 and December 2004. Inclusion and exclusion criteria are listed in Table Table11.