Enhanced coagulation activation by in vitro lipopolysaccharide challenge in patients with ventricular fibrillation complicating acute myocardial infarction. (2005 Aug)
enhanced coagulation activation by in vitro lipopolysaccharide challenge in patients with ventricular fibrillation complicating acute myocardial infarction . background : indicators of coagulation and inflammation are elevated in patients with coronary heart disease . A role of coagulation activation in ventricular fibrillation during acute myocardial infarction has not been described . methods AND results : whole blood samples of 21 patients with a history of acute myocardial infarction complicated by ventricular fibrillation and whole blood samples of 18 patients without ventricular fibrillation were incubated with lipopolysaccharide ( LPS ) . In both groups , the in vitro blood coagulation time was measured with the reorox , a viscometric whole blood coagulometer . cd62p expression on platelets , tissue factor binding on monocytes , and platelet monocyte aggregates were measured with flow cytometry . without LPS , no difference in the coagulation times were observed in both patient groups . after incubation with LPS , patients with a history of ventricular fibrillation showed a significantly decreased coagulation time compared to patients without ventricular fibrillation . The decrease of coagulation time after incubation with LPS also differed significantly in both groups . expression of cd62p on platelets was significantly higher in patients with a history of ventricular fibrillation after incubation with LPS . although in each patient group incubation with LPS induced a significantly increased amount of tissue factor on monocytes and a significantly increased the number of platelet monocyte aggregates , the two groups did not differ significantly concerning tissue factor …

The P selectin , tissue factor , coagulation triad. (2005 Aug)
The P selectin , tissue factor , coagulation triad . The primary importance of tissue factor ( TF ) in blood coagulation and thrombus propagation has been recognized for many years . nevertheless , our view about the origin of TF activity , necessary for normal hemostasis and found in pathologic conditions , needs to be revised in the light of recent observations . pioneering work by Yale nemerson s group showed that circulating TF on microparticles ( MPs ) , could promote thrombus growth . The origin and characteristics of this blood borne TF are targets of intense research as well as intense debate . surprising observations now implicate the adhesion receptor P selectin ( P sel ) , known for its role in inflammation , in these MPs generation . P sel , translocated from granules to the cell surfaces of activated platelets and endothelial cells , was recently found to play multiple roles in hemostasis . expressed on endothelium , it can mediate platelet rolling . signaling by P sel through its receptor on leukocytes , P selectin glycoprotein ligand 1 ( PSGL 1 ) , induces the generation of TF positive , highly procoagulant MPs . In addition , P sel on activated platelets helps to recruit these MPs specifically to thrombi . In this review , we discuss the roles of P sel and TF positive MPs and highlight strategies to modulate hemostasis by modulating the P sel , TF , coagulation triad .

The single nucleotide polymorphism ser128arg in the E selectin gene is associated with enhanced coagulation during human endotoxemia. (2005 Mar)
The single nucleotide polymorphism ser128arg in the E selectin gene is associated with enhanced coagulation during human endotoxemia . The single nucleotide polymorphism ( SNP ) ser128arg in the E selectin gene is overrepresented in certain patient groups with atherosclerosis or restenosis . We hypothesized and tested whether it may affect cytokine induced levels of soluble ( s ) E selectin , or be associated with proinflammatory or procoagulant properties in a well standardized inflammation model . healthy male volunteers ( n 157 ) received a lipopolysaccharide ( LPS ) infusion and were genotyped for the s128r SNP , and outcome parameters were measured by enzyme immunoassays and real time polymerase chain reaction ( RT PCR , taqman ) . The s128r SNP had no pronounced effects on basal or inducible sE selectin levels , or levels of tumor necrosis factor or interleukin 6 . however , carriers of the s128r SNP had 20 higher monocyte counts at 24 hours after LPS infusion . importantly , the s128r allele enhanced thrombin generation by 50 to 80 , as measured by prothrombin fragment F ( 1 2 ) ( P . 01 ) , and hence fibrin formation ( D dimer ) 2 fold ( P . 01 to P . 002 ) . however , tissue factor ( TF ) mRNA levels were not affected . The s128r E selectin genotype is associated with procoagulant effects in a human model of endotoxin induced , TF triggered coagulation . This could …

Neopterin induces pro atherothrombotic phenotype in human coronary endothelial cells. (2006 Sep)
neopterin induces pro atherothrombotic phenotype in human coronary endothelial cells . background : inflammation plays a pivotal role in atherothrombosis . recent data indicate that serum levels of neopterin , a marker of inflammation and immune modulator secreted by monocytes / macrophages , are elevated in patients with acute coronary syndromes and seem to be a prognostic marker for major cardiovascular events . The aim of the present study was to determine whether neopterin might affect the thrombotic and atherosclerotic characteristics of human coronary artery endothelial cells ( hcaecs ) . methods AND results : In hcaecs , neopterin induced TF mRNA transcription as demonstrated by real time polymerase chain reaction and expression of functionally active tissue factor ( TF ) as demonstrated by procoagulant activity assay , and of cellular adhesion molecules ( CAMs ) as demonstrated by FACS analysis , in a dose dependent fashion . these neopterin effects were prevented by lovastatin , a HMG CoA reductase inhibitor . neopterin induced TF and CAMs expression was mediated by oxygen free radicals through the activation of the transcription factor , nuclear factor kappa B ( NF kappab ) , as demonstrated by electrophoretic mobility shift assay and by suppression of CAMs and TF expression by superoxide dismutase and by NF kappab inhibitor , pyrrolidine dithio carbamate ammonium . conclusions : these data indicate that neopterin exerts direct effects on hcaecs by promoting CAMs and TF expression and support the hypothesis that neopterin , besides representing a marker of …

Expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo. (1996 Sep)
expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo . The pathogenesis of venous leg ulcers is based on the leakage of fibrinogen leading to a pericapillary fibrin cuff and plugging of capillaries by white blood cells . On the basis of a previous work , we had assumed that the key event in the pathogenesis of venous leg ulcers is related to inflammation generated by activated white blood cells that accumulate under unrelieved blood pressure , because in ulcer biopsies we had detected the presence of tumor necrosis factor alpha ( TNF alpha ) in intracapillary monocytes , elastase in the polymorphonuclear leukocytes near the vessels , and a pericapillary undegraded fibrin cuff causing a diffusion barrier to oxygen . This concept was developed because TNF alpha synthesized by activated monocytes is responsible for many deleterious effects . It has a potent mitogenic effect on fibroblasts , leading to new collagen deposition and angiogenesis , it induces an increase in collagenase production , it acts through upregulation of an intracellular adhesion molecule ( ICAM 1 ) , leading to leukocyte sequestration and consequently a release of toxic metabolites by the polymorphonuclear cells , an early step in chronic inflammation , it activates the coagulation pathway via a marked increase in monocyte associated tissue factor ( TF ) procoagulant activity , and it inhibits fibrinolysis by promoting the release of PAI 1 , contributing to undegraded fibrin deposition . therefore , …

Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells. (1993 Aug)
dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells . stimulation of monocytic cells by inflammatory agents such as bacterial lipopolysaccharide or tumour necrosis factor alpha leads to the rapid and transient expression of tissue factor , the major cellular initiator of the extrinsic coagulation cascade in both haemostasis and tissue inflammation . In this study we investigated whether the synthetic anti inflammatory glucocorticoid , dexamethasone , would inhibit agonist induction of tissue factor expression in both monocytes and endothelial cells . surprisingly , dexamethasone significantly enhanced the induction of tissue factor expression by peripheral blood mononuclear cells and an established monocytic cell line , THP 1 , in response to lipopolysaccharide or tumour necrosis factor alpha . however , unlike monocytic cells , dexamethasone did not enhance agonist induction of tissue factor in endothelial cells . synergistic enhancement of tissue factor expression by dexamethasone was also reflected in tissue factor mRNA levels in THP 1 cells , but was not the result of improved TF mRNA stability . synergism between bacterial lipopolysaccharide and glucocorticoid in the induction of monocyte effector function is extremely unusual and may help to explain the variable outcome of glucocorticoid treatment of septic shock .

C reactive protein induces human peripheral blood monocytes to synthesize tissue factor. (1993 Aug)
C reactive protein induces human peripheral blood monocytes to synthesize tissue factor . The acute inflammatory response is frequently accompanied by serious thrombotic events . We show that C reactive protein ( CRP ) , an acute phase reactant that markedly increases its serum concentration in response to inflammatory stimuli , induced monocytes to express tissue factor ( TF ) , a potent procoagulant . purified human CRP in concentrations commonly achieved in vivo during inflammation ( 10 to 100 micrograms / mL ) induced a 75 fold increase in TF procoagulant activity ( PCA ) of human peripheral blood mononuclear cells ( PBM ) , with a parallel increase in TF antigen levels . CRP induced PCA was completely blocked by a monoclonal antibody against human TF but not by irrelevant murine IgG . Dot blot analysis showed a significant increase of TF mRNA after 4 hours of incubation with CRP , followed by a peak of PCA within 6 and 8 hours . actinomycin D and cycloheximide blocked CRP stimulated PCA , suggesting that de novo TF protein synthesis was required . endotoxin ( LPS ) contamination of CRP was excluded as the mediator of TF synthesis because : ( 1 ) CRP was limulus assay negative ; ( 2 ) induction of TF PCA by CRP was not blocked by polymyxin B , in contrast to LPS induced PCA ; ( 3 ) antihuman CRP IgG inhibited CRP induced PCA , but not LPS induced PCA ; …

Effects of alpha 1 acid glycoprotein on tissue factor expression and tumor necrosis factor secretion in human monocytes. (1997 Jan)
effects of alpha 1 acid glycoprotein on tissue factor expression and tumor necrosis factor secretion in human monocytes . activated monocytes express tissue factor ( TF ) and secrete tumor necrosis factor alpha ( TNF alpha ) , which are important in the initiation of blood coagulation and inflammation . We investigated the effect of alpha 1 acid glycoprotein ( alpha 1 AGP ) , an acute phase protein , on the induction of the expression of TF and the secretion of TNF alpha in human monocytes in vitro . The TF activity of both fresh human monocytes and human monocytic cell line U937 significantly increased in a dose dependent manner after a 6 h incubation with human or bovine alpha 1 AGP . The activity of TF gradually tailed off after 24 h . RT PCR and southern blot analysis revealed that TF mRNA synthesis was induced in monocytes . inhibition of alpha 1 AGP induced TF expression by actinomycin D ( ActD ) further support that de novo TF mRNA synthesis was required . The specificity of the alpha 1 AGP induced TF activity was demonstrated by anti alpha 1 AGP antibody inhibition . TNF alpha secretion in alpha 1 AGP stimulated monocytes was also increased ; this could be blocked by pentoxifylline ( PTX ) . The possible contamination of lipopolysaccharide ( LPS ) in the alpha 1 AGP was excluded by limulus amoebocyte lysate . therefore , these results indicate that alpha 1 AGP may contribute …

Tissue factor and factor VIIa receptor / ligand interactions induce proinflammatory effects in macrophages. (1999 Nov)
tissue factor and factor VIIa receptor / ligand interactions induce proinflammatory effects in macrophages . The potential for tissue factor ( TF ) to enhance inflammation by factor VIIa dependent induction of proinflammatory changes in macrophages was explored . purified recombinant human factor VIIa enhanced reactive oxygen species production by human monocyte derived macrophages expressing TF in vitro . This effect was dose and time dependent , ligand and receptor specific , and independent of other coagulation proteins . This receptor / ligand binding induced phospholipase C dependent intracellular calcium fluxes . transfection studies using a human monocyte derived cell line ( U937 ) demonstrated that an intact intracytoplasmic domain of TF is required for factor VIIa induced intracellular calcium fluxes . The capacity of TF to enhance proinflammatory functions of rabbit peritoneal elicited macrophages ( production of reactive oxygen species and expression of major histocompatibility complex class II and cell adhesion molecules ) was demonstrated in vivo by treatment with an anti TF antibody . these data demonstrate that , in addition to its role in activation of coagulation , TF can directly augment macrophage activation . these effects are initiated by binding factor VIIa and are independent of other coagulation proteins . these studies provide the first demonstration of a direct proinflammatory role for TF acting as a cell signaling receptor .

Macrophage containing factor XIII subunit a in salivary glands of patients with sjögren s syndrome. (1994 Feb)
macrophage containing factor XIII subunit a in salivary glands of patients with sjögren s syndrome . minor labial salivary glands obtained at biopsy from patients with sjögren s syndrome were investigated by immunomorphological methods for the presence of monocyte derived macrophages . according to our observations published earlier the immunomorphological detection of factor XIII subunit a is a useful marker for recognizing cells of monocyte / macrophage lineage . factor XIII subunit a was detected by a highly sensitive immunoperoxidase staining , and cells containing this coagulation enzyme were characterized by double immunofluorescence stainings . factor XIII subunit a cells were found to be highly accumulated at the interface of normal tissue and peritubular infiltrate . In double immunofluorescence labelling systems factor XIII subunit a cells were simultaneously labelled by RFD7 and Dako antimacrophage monoclonal antibodies . They also expressed HLA DR antigen as revealed by a reaction with rfdr2 monoclonal antibody . The results suggest that monocyte derived tissue macrophages are present in salivary glands of patients with sjögren s syndrome and have a characteristic distribution . It can be assumed that they have a role in the demarcation of peritubular inflammation and thus have an effect on the progression of the disease .

Inhibition of the tissue factor thrombin pathway limits infarct size after myocardial ischemia reperfusion injury by reducing inflammation. (2000 Dec)
inhibition of the tissue factor thrombin pathway limits infarct size after myocardial ischemia reperfusion injury by reducing inflammation . functional inhibition of tissue factor ( TF ) has been shown to improve coronary blood flow after myocardial ischemia / reperfusion ( I / R ) injury . TF initiates the coagulation protease cascade , resulting in the generation of the serine protease thrombin and fibrin deposition . thrombin can also contribute to an inflammatory response by activating various cell types , including vascular endothelial cells . We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I / R injury . At risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes , which was associated with a low level of extravascular fibrin deposition . functional inhibition of TF activity with an anti rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61 ( P 0 . 004 ) and 44 ( P 0 . 014 ) , respectively . similarly , we found that inhibition of thrombin with hirudin reduced infarct size by 59 ( P 0 . 014 ) . In contrast , defibrinogenating the rabbits with ancrod had no effect on infarct size , suggesting that fibrin deposition does not significantly contribute to infarct size . functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration . We propose that cardiomyocyte …

Synergistic induction of tissue factor by coagulation factor Xa and TNF : evidence for involvement of negative regulatory signaling cascades. (2005 Aug)
synergistic induction of tissue factor by coagulation factor Xa and TNF : evidence for involvement of negative regulatory signaling cascades . enzymes of the blood coagulation pathway enhance the inflammatory response leading to endothelial dysfunction , accounting , in part , for the vascular complications occurring in sepsis and cardiovascular disease . The responses of endothelial cell activation include induction of the expression of tissue factor ( TF ) , a membrane glycoprotein that promotes thrombosis , and of E selectin , a cell adhesion molecule that promotes inflammation . In this report , we demonstrate synergistic interactions between the coagulation factor Xa ( fXa ) and the proinflammatory cytokines TNF , IL 1beta , and cd40l , leading to enhanced expression of TF and E selectin in endothelial cells . A detailed analysis of the molecular pathways that could account for this activity of fXa showed that fXa inhibited the cytokine induced expression of dual specificity phosphatases , MAP kinase phosphatase L , 4 , 5 , and 7 , blocking a negative regulatory effect on c Jun N terminal kinase . The synergistic interaction between fXa and TNF was also involved in the inhibition of A20 and ikappabalpha expression in the ikappab kinase NF kappab pathway . The data indicate that inhibition of negative regulatory signaling accounts for the amplification of cytokine induced endothelial cell activation by fXa .

Potent and selective kunitz domain inhibitors of plasma kallikrein designed by phage display. (1995 Dec)
potent and selective kunitz domain inhibitors of plasma kallikrein designed by phage display . phage displaying APPI kunitz domain libraries have been used to design potent and selective active site inhibitors of human plasma kallikrein , a serine protease that plays an important role in both inflammation and coagulation . selected clones from two kunitz domain libraries randomized at or near the binding loop ( positions 11 13 , 15 19 , and 34 ) were sequenced following five rounds of selection on immobilized plasma kallikrein . invariant preferences for Arg at position 15 and His at position 18 were found , whereas His , Ala , Ala , and Pro were highly preferred residues at positions 13 , 16 , 17 , and 19 , respectively . At position 11 Pro , Asp , and Glu were favored , while hydrophobic residues were preferred at position 34 . selected variants , purified by trypsin affinity chromatography and reverse phase high performance liquid chromatography , potently inhibited plasma kallikrein , with apparent equilibrium dissociation constants ( Ki ) ranging from approximately 75 to 300 pM . From sequence and activity data , consensus mutants were constructed by site directed mutagenesis . One such mutant , KALI DY , which differed from APPI at 6 key residues ( T11D , P13H , M17A , I18H , S19P , and F34Y ) , inhibited plasma kallikrein with a Ki 15 / 14 pM , representing an increase in binding affinity of more …

Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. (2002 May)
extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide . initiation of coagulation by tissue factor ( TF ) is a potentially powerful regulator of local inflammatory responses . We hypothesized that blockade of TF factor VIIa ( fviia ) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation of escherichia coli lipopolysaccharide ( LPS 0111 : B4 ) . At the time of injury , rats received one dose of site inactivated fviia ( FFR fviia ) or saline intravenously . At 0 , 6 , 12 , 24 , and 48 h after injury , lungs were examined for histologic changes and bronchoalveolar lavage ( BAL ) was performed to assess protein , lactate dehydrogenase ( LDH ) activity , cell counts , and cytokine levels . LPS injured rats treated with FFR fviia showed decreased intra alveolar inflammation and fibrin deposition by light microscopy compared with untreated rats . This was accompanied by decreased protein leakage ( P 0 . 0001 ) , LDH activity ( P 0 . 0001 ) , and local elaboration of interleukin ( IL ) 1beta , IL 6 , and IL 10 ( all P 0 . 0001 ) , but not tumor necrosis factor ( TNF ) alpha . protection was associated with reduction of TF mRNA expression in whole lung , but not with changes in nuclear translocation of nuclear factor ( NF ) kappab . FFR fviia given 6 h after …

Effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation. (2002 Oct)
effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation . anticoagulants have gained increasing attention in the treatment of sepsis . This study used danaparoid to investigate the role of factor Xa in endotoxin induced coagulation and inflammation and its effectiveness when coagulation activation has already occurred . thirty healthy volunteers were enrolled in the randomized , placebo controlled trial . subjects received 2 ng / kg endotoxin and danaparoid 10 min or 3 h thereafter or placebo . endotoxin increased prothrombin fragment 1 2 ( F ( 1 2 ) ) levels from 0 . 5 to 7 . 0 nmol / L at 5 h in the placebo group . early danaparoid infusion inhibited endotoxin induced thrombin formation : maximum F ( 1 2 ) levels reached only 1 . 8 nmol / L ( P . 01 , vs . baseline or placebo ) . delayed danaparoid infusion effectively blocked further thrombin formation . however , danaparoid did not alter endotoxin induced changes in the fibrinolytic system , cytokine levels , activation of leukocytes , or tissue factor expression on monocytes . danaparoid therefore selectively attenuates endotoxin induced coagulopathy , even with delayed administration when coagulation activation is well under way .

Coagulation blockade prevents sepsis induced respiratory and renal failure in baboons. (2001 Dec)
coagulation blockade prevents sepsis induced respiratory and renal failure in baboons . sepsis induced tissue factor ( TF ) expression activates coagulation in the lung and leads to a procoagulant environment , which results in fibrin deposition and potentiates inflammation . We hypothesized that preventing initiation of coagulation at TF factor VIIa ( fviia ) complex would block fibrin deposition and control inflammation in sepsis , thereby limiting acute lung injury ( ALI ) and other organ damage in baboons . A model of ALI was used in which adult baboons were primed with killed escherichia coli ( 1 x 10 ( 9 ) CFU / kg ) , and bacteremic sepsis was induced 12 h later by infusion of live E . coli at 1 x 10 ( 10 ) CFU / kg . animals in the treatment group were given a competitive inhibitor of TF , site inactivated fviia ( fviiai ) , intravenously at the time of the infusion of live bacteria and monitored physiologically for another 36 h . fviiai dramatically protected gas exchange and lung compliance , prevented lung edema and pulmonary hypertension , and preserved renal function relative to vehicle ( all p 0 . 05 ) . treatment attenuated sepsis induced fibrinogen depletion ( p 0 . 01 ) and decreased systemic proinflammatory cytokine responses , for example , interleukin 6 ( p 0 . 01 ) . The protective effects of TF blockade in sepsis induced ALI were confirmed by using tissue …

The prothrombotic state in cancer : pathogenic mechanisms. (2004 Jun)
The prothrombotic state in cancer : pathogenic mechanisms . thrombosis and disseminated intravascular coagulation ( DIC ) are common complications in cancer . patients with malignancy have a prothrombotic state due to the ability of almost all type of cancer cells to activate the coagulation system . however , none of the haemostatic markers of coagulation has any predictive value for the occurrence of the thrombotic events in one individual patient . The pathogenesis of the prothrombotic state in cancer is complex and , probably , multifactorial . prothrombotic factors in malignancy include the tumour production of procoagulants ( i . e . , tissue factor ( TF ) and cancer procoagulant ( CP ) ) and inflammatory cytokines , and the interaction between tumour cells and blood ( i . e . , monocytes / macrophages , platelets ) and endothelial cells . other mechanisms of thrombus promotion include some general responses of the host to the tumour ( i . e . , acute phase , inflammation , angiogenesis ) , decreased levels of inhibitors of coagulation , and impaired fibrinolysis . In addition , the prothrombotic tendency of cancer patients is enhanced by anticancer therapy , such as surgery , chemotherapy , hormone therapy and radiotherapy , by indwelling central venous catheter , and by haemodinamic compromise ( i . e . , stasis ) . however , not all of the mechanisms allowing the prothrombotic state of cancer are entirely understood . therefore , it is …

Effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors. (1997 Apr)
effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors . background : delayed xenograft rejection ( DXR ) is characterized by inflammation and vascular thrombosis . activation of coagulation may occur as a result of tissue factor ( TF ) expression on both activated donor endothelial cells ( EC ) and recipient infiltrating monocytes ( Mo ) . In addition , natural anticoagulants associated with porcine endothelial cells may not function adequately across species . methods : In the present study , we examined the interaction of the TF pathway of coagulation with the natural anticoagulant TF pathway inhibitor , in xenogeneic leukocyte EC cultures in vitro , and during rejection of discordant xenografts in vivo . results : coculture of human Mo with pig aortic EC ( PAEC ) resulted in 1 . 7 fold and 2 fold higher induction of Mo TF and Mo intercellular adhesion molecule 1 , respectively , when compared with coculture with human aortic endothelial cells ( HAEC ) . In addition , TF dependent and independent activation of coagulation factor X was higher on PAEC than on HAEC . Low levels of mRNA for tissue factor pathway inhibitor ( TFPI ) and its variant , TFPI 2 , in resting PAEC were up regulated by stimulation with tumor necrosis factor alpha . procoagulant activity of recombinant human TF complexed to activated factor VII was inhibited by PAEC and HAEC associated TFPI by 22 and 56 , respectively . In contrast …

Emerging insights in tissue factor dependent signaling events. (2006 Feb)
emerging insights in tissue factor dependent signaling events . The complex of the cell surface receptor tissue factor ( TF ) and its ligand coagulation factor VIIa ( fviia ) is the primary initiator of the coagulation cascade . It is now clear the TF initiated coagulation pathway also plays major nonhemostatic roles in inflammation , tumor growth , and angiogenesis . direct or indirect cell signaling by TF fviia or downstream coagulation proteases is an essential part of these nonhemostatic functions . The TF fviia complex activates protease activated receptor 2 and thus regulates gene transcription and protein translation , cell proliferation and survival , or cell motility and integrin activation . In this review , we relate our current understanding of direct TF signaling pathways to the emerging roles of TF in ( patho ) physiology .

Tissue factor in infection and severe inflammation. (2006 Feb)
tissue factor in infection and severe inflammation . In the pathogenesis of vascular disease , inflammation and coagulation play a pivotal role . increasing evidence points to an extensive cross talk between these two systems , whereby inflammation not only leads to activation of coagulation , but coagulation also considerably affects inflammatory activity . tissue factor ( TF ) plays an important role at the crossroad of coagulation and inflammation , as the principal initiator of coagulation and an important modulator of inflammation . proinflammatory cytokines can induce TF expression on mononuclear cells and endothelial cells and thereby commence pathways that lead to thrombin generation . simultaneously , TF may bind to cellular receptors , which may affect the production and release of inflammatory mediators . there is increasing experimental evidence that TF inhibition may have beneficial effects in disease states in which the combination of coagulation and inflammation plays a prominent role .