Subscribe to RSS
DOI: 10.1055/s-0038-1653884
Sites of Tissue Factor Pathway Inhibitor (TFPI) and Tissue Factor Expression under Physiologic and Pathologic Conditions
On behalf of the Subcommittee on Tissue Factor Pathway Inhibitor (TFPI) of the Scientific and Standardization Committee of the ISTHPublication History
Publication Date:
09 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199505/lookinside/thumbnails/10-1055-s-0038-1653884-1.jpg)
Summary
Under normal conditions, TFPI expression is restricted to megakaryocytes and the endothelium of the microvasculature. It is not synthesized by normal hepatocytes or by the endothelium of larger vessels. In contrast, endothelium and peripheral blood cells do not express tissue factor under normal conditions. Expression of tissue factor under normal physiologic conditions is widespread and is localized in areas which are physically separated from the circulating blood. During an inflammatory response, circulating monocytes have been shown to express tissue factor, whereas in general, expression of tissue factor has not been observed in the endothelium. Adherent monocytes/macrophages express both tissue factor and TFPI under pathologic conditions. Whether or not circulating peripheral blood monocytes under inflammatory conditions express TFPI is not known.
-
References
- 1 Rapaport SI, Rao LV M. Initiation and regulation of tissue factor-dependent blood coagulation. Arteriosclerosis and Thrombosis 1992; 12: 1111-1121
- 2 Østerud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: Additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 1977; 74: 5260-5264
- 3 Zur M, Nemerson Y. Kinetics of factor IX activation via the extrinsic pathway. J Biol Chem 1980; 255: 5703-5707
- 4 Sandset PM, Wam-Cramer BJ, Rao LV M, Maki SI, Rapaport SI. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intra-vascular coagulation induced with tissue factor: Evidence supporting a physiologic role for EPI as a natural anticoagulant. Proc Natl Acad Sci USA 1991; 88: 708-712
- 5 Sandset PM, Wam-Cramer BJ, Maki SI, Rapaport SI. Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. Blood 1991; 78: 1496-1502
- 6 Ruf W, Edgington TS. Structural biology of tissue factor, the initiator of thrombogenesis in vivo. FASEB J 1994; 8: 385-390
- 7 Harlos K, Martin DM, O’Brien DP, Jones EY, Stuart DI, Polikarpov I, Miller A, Tuddenham EG, Boys CW G. Crystal structure of the extracellular region of human tissue factor. Nature 1994; 370: 662-666
- 8 Wun T-C, Kretzmer KK, Girard TJ, Miletich JP, Broze Jr GJ. Cloning and characterization of a cDNA coding for the lipopprotein-associated coagulation inhibitor shows that it consists of three tandom Kunitz inhibitory domains. J Biol Chem 1988; 263: 6001-6004
- 9 van derLogt, Reitsma PH, Bertina RM. Intron-exon organization of the human gene coding for the lipoprotein-associated coagulation inhibitor: The factor Xa dependent inhibitor of the extrinsic pathway of coagulation. Biochemistry 1991; 30: 1571-1577
- 10 Girard TJ, Eddy R, Wesselschmidt RL, MacPhail LA, Likert KM, Byers MG, Shows TB, Broze Jr GJ. Structure of the human lipoprotein-associated coagulation inhibitor gene. J Biol Chem 1991; 266: 5036-5041
- 11 Envoji K-I, Emi M, Mukai T, Imada M, Leppert ML, Lalouel JM, Kato H. Human tissue factor inhibitor (TFPI) gene: Complete genomic structure and localization on the genetic map of chromosome 2q. Genomics 1993; 17: 423-428
- 12 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990; 29: 7539-7546
- 13 Hamamoto T, Yamamoto M, Nordfang OPetersen, Foster DC, Kisiel W. Inhibitory properties of full-length and truncated recombinant tissue factor pathway inhibitor (TFPI)Evidence that the third Kunitz-type domain of TFPI is not essential for the inhibition of factor Vlla-tissue factor complexes on cell surfaces. J Biol Chem 1993; 268: 8704-8710
- 14 Nordfang O, Bjøm SE, Valentin S, Nielsen LS, Wildgoose P, Beck TC, Hedner U. The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991; 30: 10371-10376
- 15 Wesselschmidt R, Likert K, Girard T, Wun T-C, Broze Jr GJ. Tissue factor pathway inhibitor: The carboxy-terminus is required for optimal inhibition of factor Xa. Blood 1992; 79: 2004-2010
- 16 Petersen JG L, Meyn G, Rasmussen JS, Petersen J, Bjørn SE, Jonassen I, Christiansen L, Nordfang O. Characterization of human tissue factor pathway inhibitor variants expressed in Saccharomyces cerevisae. J Biol Chem 1993; 268: 13344-13351
- 17 Sprecher CA, Kisiel W, Mathews S, Foster DC. Molecular cloning expression and partial characterization of a second human tissue-factorpathway inhibitor. Proc Natl Acad Sei 1994; 91: 3353-3357
- 18 Miyaga Y, Koshikawa N, Yasumitsu H, Miyagi E, Hirahara A, Kazuaki M, Umeda M, Miyazaki K. cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: Identification as placental protein 5 and tissue factor pathway inhibitor-2. J Biochem 1994; 116: 939-942
- 19 Bajaj MS, Ameri A, Bajaj SP. Tissue factor pathway inhibitor - A regulator of tissue factor induced coagulation. In: Anticoagulants: Physiologic, Pathologic, and Pharmacologic. David Green. ed CRC Press Boca Raton; 1994: 41-65
- 20 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues: Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 86: 1087-1097
- 21 Fleck RA, Rao LV, Rapaport SI, Varki N. Localization of tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res 1990; 57: 765-781
- 22 Østerud B, Tindall A, Brox JH, Olsen JO. Thromboplastin content of the vessel walls of different arteries and organs of rabbits. Thromb Res 1986; 42: 323-329
- 23 Werling RW, Zaccharski LR, Kisiel W, Bajaj SP, Memoli VA, Rousseau SM. Distribution of tissue factor pathway inhibitor in normal and malignant human tissues. Thromb Haemost 1993; 69: 366-369
- 24 Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP. Cultured normal hepatocytes do not synthesize lipoprotein-associated coagulation inhibitors: Evidence that endothelium is the principal site of its synthesis. Proc Nad Acad Sci USA 1990; 87: 8869-8873
- 25 Bajaj MS, Kuppuswamy MN, Leingang K, Bajaj SP. Transcriptional expression of tissue factor pathway inhibitor in normal human tissues. Blood 1993; 82 Suppl (Suppl. 11) 1071a
- 26 Colluci M, Balconi G, Lorenzet R, Pietra A, Locati D. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
- 27 Brox JH, Østerud B, Bjørklid E, Fenton JW. Production and availability of thromboplastin in endothelial cells: The effects of thrombin, endotoxin and platelets. Br J Haematol 1984; 57: 239-246
- 28 Bevilacqua HP, Pober JS, Majeau GR, Cotran RS, Gimbrone MA. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells cultured with endothelial with endothelial cell growth factor and heparin. J Exp Med 1984; 160: 618-623
- 29 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone Jr MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterization and comparison with the actions of interleukin-1. Proc Natl Acad Sci USA 1986; 83: 4533-4537
- 30 Solberg S, Østerud B, Larsen T, Sørlie D. Lack of ability to synthesize tissue factor by endothelial cells in intact human saphenous veins. Blood Coagulation Fibrinolysis 1990; 1: 595-600
- 31 Drake TA, Chen J, Chang A, Taylor Jr FB. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal E.coli sepsis. Am J Pathol 1993; 142: 1458-1470
- 32 Rivers RP, Hathaway WE, Weston WL. The endotoxin-induced coagulant activity of human monocytes. Br J Haematol 1975; 30: 311-315
- 33 Kornberg A, Treves A, Rachmiliwitz EA, Fibach E. Generation of procoagulant activity (PCA) by phorbol-ester-induced macrophage derived from a leukemic promyelocytic cell line (HL-60). Blood 1982; 59: 1061-1066
- 34 Conkling PR, Greenburg CS, Weinburg JB. Tumor necrosis factor induces tissue factor like activity in human leukaemic cell line U937 and peripheral blood monocytes. Blood 1988; 72: 128-133
- 35 Carlsen E, Fiatmark A, Prydz H. Cytokine-induced procoagulant activity in monocytes and endothelial cells. Transplantation 1988; 46: 575-580
- 36 Prydz H, Lyberg T, Deteix P, Allison AC. In vitro stimulation of tissue thromboplastin (factor III) activity in human monocytes by immune complexes and lectins. Thromb Res 1979; 15: 465-474
- 37 Pernod G, Polack B, Peyron F, Luisy A, Kolodie L, Ambroise-Thomas P, Santoro F. Monocyte tissue factor expression induced by plasmodium falciparum-infected erythrocytes. Thromb Haemost 1992; 68: 111-114
- 38 Østerud B, Eskeland T. The mandatory role of complement in the endotoxin-induced synthesis of tissue thromboplastin in blood monocytes. FEBS Letters 1982; 149: 75-79
- 39 Halvorsen H, Olsen JO, Østerud B. Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets. J Leuk Biol 1983; 54: 275-282
- 40 Østerud B, Flaegstad T. Increased thromboplastin activity in monocytes of patients with meningococcal infection: Related to an unfavourable prognosis. Thromb Haemost 1983; 49: 5-7
- 41 Almdahl SM, Brox JH, Østerud B. Mononuclear phagocyte thromboplastin and endotoxin in patients with secondary bacterial peritonitis. Scand J Gastroenterol 1987; 22: 914-918
- 42 Kjæve J, Østerud B. The function of alveolar macrophages and granulocytes in rabbits endotoxemia. Effect of methylprednisolone Acta Anaestesiol Scand 1990; 34: 619-623
- 43 Ameri A, Kuppuswamy MN, Basu S, Bajaj SP. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators. Blood 1992; 79: 3219-3226
- 44 Rana SV, Reimers HJ, Pathikonda MS, Bajaj SP. Expression of tissue factor and factor VIIa/tissue factor activity in endotoxin or phorbol stimulated U 937 monocyte-like cells. Blood 1988; 71: 259-262
- 45 Bajaj MS, Ameri A, Kuppuswamy MN, Bajaj SP. Expression of tissue factor pathway inhibitor (TFPI) and GATA-2 transcription factor by activated human monocytes. Blood 1993; 82: 343a
- 46 van der Logt CP E, Dirven RJ, Reitsma PH, Bertina RM. Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester. Blood Coagulation Fibrinolysis 1994; 5: 211-220
- 47 McGee MP, Foster S, Wang X. Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytesA potential mechanism for localized control of blood coagulation. J Exp Med 1994; 179: 1847-1854
- 48 Sabharwal AK, Bajaj SP, Ameri A, Tricomi SM, Hyers TM, Dahms TE, Taylor FBJ, Bajaj SM. Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. Am J Resp Crit Care Med 1995; 151: 758-767
- 49 Ishii H, Salem HH, Bell CE, Laposata EA, Majerus PW. Thrombomodulin, man endothelial anticoagulant protein is absent from the human brain. Blood 1986; 67: 362-365
- 50 van Nostrand WW, Schmaier AH, Wagner SL. Potential role of protease nexin-2/amyloid beta-protein precursor as a cerebral anticoagulant (Review). Ann New York Acad Sei 1992; 674: 243-252