The effect of tissue factor pathway inhibitor on hepatic ischemic reperfusion injury of the rat.

BACKGROUND Tissue factor (TF) is an initiation factor for blood coagulation, and its expression is induced on macrophages and endothelial cells during the inflammatory or immune responses. In a previous study, we reported the significance of TF expression in hepatic ischemic reperfusion injury using a rat model. Recently, tissue factor pathway inhibitor (TFPI) has been discovered, and the effect of TFPI has been assessed in vivo. In this study, therefore, we studied the effect of TFPI on hepatic ischemic reperfusion injury of the rat. METHODS After laparotomy of Lewis rats, the branches of the hepatic artery and portal vein leading to the median, left, and caudate lobes of the liver were clamped. The liver was reperfused after 120 or 180 min of ischemia. Simultaneously, recombinant human TFPI (4 mg/kg) was injected via a superiomesenteric vein. Rats were sacrificed at 5, 12, and 24 hr after reperfusion, and liver tissues were harvested. TF expression was studied by immunohistochemical staining with the monoclonal antibody (HTF-K108). RESULTS Survival rates over a 5-day period were examined after the ischemic time of 120 and 180 min. Seven of 10 rats in the 120-min ischemia group (n=10), and only 1 (10%) rat of 10 in the 180-min ischemia group (n=10) survived. However, by the treatment with TFPI, all of the rats in the 120-min ischemia group (n=10), and six rats in the 180-min ischemia group (n=10) survived (P<0.05). The serum concentrations of alanine aminotransferase (ALT) and thrombin-antithrombin complex (TAT) before ischemia were 30.0+/-2.3 IU/L and 4.7+/-1.4 ng/ml, respectively (n=5). These levels showed a peak at 3-5 hr after reperfusion (ALT: 13909+/-1900 IU/L, TAT: 30.4+/-7.0 ng/ml) (P<0.01). However, both peak levels were decreased by the treatment with TFPI (ALT: 6017+/-1290 IU/L, TAT: 5.4+/-2.1 ng/ml) (P<0.01). Although TF was strongly stained on endothelial cells and Kupffer cells accumulating to the site of the necrosis in the control group, the area of the necrosis and the grade of TF staining were significantly reduced in the TFPI-treated group. CONCLUSIONS These results indicated that TFPI strongly inhibited the injury of the ischemic reperfusion, and confirmed that TF played a pivotal role in the development of ischemic reperfusion injury.

[1]  H. Yamagishi,et al.  Expression of tissue factor in hepatic ischemic-reperfusion injury of the rat. , 1998, Transplantation.

[2]  K. Boudjema,et al.  Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers. , 1998, Transplant immunology.

[3]  I. Anegon,et al.  Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells. , 1997, Transplantation.

[4]  Y. Kamikubo,et al.  Human recombinant tissue‐factor pathway inhibitor prevents the proliferation of cultured human neonatal aortic smooth muscle cells , 1997, FEBS letters.

[5]  J. Wallwork,et al.  Pig-to-primate cardiac xenotransplantation and cyclophosphamide therapy. , 1997, Transplantation proceedings.

[6]  A. Lindahl,et al.  Tissue factor pathway inhibitor: from unknown coagulation inhibitor to major antithrombotic principle. , 1997, Cardiovascular research.

[7]  J. Platt,et al.  Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. , 1997, Transplantation.

[8]  D. Candinas,et al.  Apyrase administration prolongs discordant xenograft survival. , 1996, Transplantation.

[9]  K. Nakagawa,et al.  Effects of recombinant human tissue factor pathway inhibitor on thrombus formation and its in vivo distribution in a rat DIC model. , 1996, American journal of clinical pathology.

[10]  J. Matsuda,et al.  Antithrombotic Effect of Human Recombinant Tissue Factor Pathway Inhibitor on Endotoxin-induced Intravascular Coagulation in Rats: Concerted Effect with Antithrombin , 1996, Thrombosis and Haemostasis.

[11]  J. Platt,et al.  Molecular barriers to xenotransplantation. , 1996, Transplantation.

[12]  D. Candinas,et al.  Inhibition of platelet integrin GPIIbIIIa prolongs survival of discordant cardiac xenografts. , 1996, Transplantation.

[13]  M. Bonneau,et al.  An experimental model for testing von Willebrand factor function: successful SLA-matched crossed bone marrow transplantations between normal and von Willebrand pigs. , 1996, Experimental hematology.

[14]  K. Boudjema,et al.  Extracorporeal immunoadsorption of xenoreactive natural antibodies in the pig/rhesus model: comparison of three methods. , 1996, Transplantation proceedings.

[15]  J. Imanishi,et al.  The anticoagulant effect of antithrombin III on hyperacute xenograft rejection. , 1996, Transplantation proceedings.

[16]  Brian Savage,et al.  Initiation of Platelet Adhesion by Arrest onto Fibrinogen or Translocation on von Willebrand Factor , 1996, Cell.

[17]  K K Wu,et al.  Platelet activation mechanisms and markers in arterial thrombosis , 1996, Journal of internal medicine.

[18]  E. Topol,et al.  Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. , 1995, Circulation.

[19]  K. Stuhlmeier,et al.  Barriers to xenotransplantation , 1995, Nature Medicine.

[20]  T. Miyata,et al.  Effect of heparin on the inhibition of factor Xa by tissue factor pathway inhibitor: a segment, Gly212-Phe243, of the third Kunitz domain is a heparin-binding site. , 1995, Biochemistry.

[21]  J. Saffitz,et al.  The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo. , 1995, The Journal of clinical investigation.

[22]  A. Dackiw,et al.  Posttranscriptional regulation of macrophage tissue factor expression by antioxidants. , 1995, Blood.

[23]  J. Platt,et al.  Transient perturbation of endothelial integrity induced by natural antibodies and complement , 1995, The Journal of experimental medicine.

[24]  K. Stuhlmeier,et al.  Endothelial Cell Activation and Thromboregulation during Xenograft Rejection , 1994, Immunological reviews.

[25]  F. Bach,et al.  Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells , 1994 .

[26]  K. Stuhlmeier,et al.  Pathways of procoagulation in discordant xenografting. , 1994, Transplantation proceedings.

[27]  J. Sadler,et al.  A Revised Classification of von Willebrand Disease , 1994, Thrombosis and Haemostasis.

[28]  K. Kawachi,et al.  Effects of a platelet-activating factor antagonist at different doses given simultaneously with double-filtration plasmapheresis on cardiac xenograft survival. , 1994, Transplantation proceedings.

[29]  F. Bach,et al.  Human xenoreactive natural antibodies--avidity and targets on porcine endothelial cells. , 1993, Transplantation.

[30]  O. Svendsen,et al.  The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits. , 1993, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[31]  D. Meyer,et al.  von Willebrand Factor: Structure and Function , 1993, Thrombosis and Haemostasis.

[32]  A. Chang,et al.  Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. , 1993, The Journal of clinical investigation.

[33]  T. Drake,et al.  Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. , 1993, The American journal of pathology.

[34]  A. Guha,et al.  Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. , 1993, The Journal of clinical investigation.

[35]  Thomas B. Tschopp,et al.  Relationship between tissue factor expression and deposition of fibrin, platelets, and leukocytes on cultured endothelial cells under venous blood flow conditions , 1993 .

[36]  H. Jaeschke,et al.  Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia. , 1993, The American journal of physiology.

[37]  P. Mannucci,et al.  Interaction of porcine von Willebrand factor with the platelet glycoproteins Ib and IIb/IIIa complex , 1992, British journal of haematology.

[38]  A. Wilson,et al.  Clearance of Recombinant Tissue Factor Pathway Inhibitor (TFPI) in Rabbits , 1992, Thrombosis and Haemostasis.

[39]  D. Cooper.  Depletion of natural antibodies in non-human primates--a step towards successful discordant xenografting in humans. , 1992, Clinical transplantation.

[40]  R. Wesselschmidt,et al.  Tissue factor pathway inhibitor: the carboxy-terminus is required for optimal inhibition of factor Xa. , 1992, Blood.

[41]  S. Rapaport,et al.  Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. , 1991, Blood.

[42]  P. Sims,et al.  The response of human platelets to activated components of the complement system. , 1991, Immunology today.

[43]  N. Mackman,et al.  Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide , 1991, Molecular and cellular biology.

[44]  J. Miletich,et al.  Purification and properties of heparin-releasable lipoprotein-associated coagulation inhibitor. , 1991, Blood.

[45]  D. Rader,et al.  Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. , 1991, Blood.

[46]  H. Jaeschke,et al.  Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. , 1991, The American journal of physiology.

[47]  J. Freyssinet,et al.  Heterogeneous regulation of constitutive thrombomodulin or inducible tissue-factor activities on the surface of human saphenous-vein endothelial cells in culture following stimulation by interleukin-1, tumour necrosis factor, thrombin or phorbol ester. , 1991, The Biochemical journal.

[48]  P. Sandset,et al.  Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[49]  C. Smith,et al.  Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[50]  H. Saito,et al.  Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[51]  T. Wun,et al.  Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. , 1990, Blood.

[52]  R. Strieter,et al.  Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. , 1990, The Journal of clinical investigation.

[53]  S. Rapaport,et al.  Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. , 1990, Blood.

[54]  H. Mohri,et al.  Isolation of the von Willebrand factor domain interacting with platelet glycoprotein Ib, heparin, and collagen and characterization of its three distinct functional sites. , 1989, The Journal of biological chemistry.

[55]  S. Gregory,et al.  Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin , 1989, Molecular and cellular biology.

[56]  Kathleen M. Smith,et al.  Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[57]  S. Rapaport,et al.  Modifications of Extrinsic Pathway Inhibitor (EPI) and Factor Xa that Affect their Ability to Interact and to Inhibit Factor Vila/Tissue Factor: Evidence for a Two-Step Model of Inhibition , 1988, Thrombosis and Haemostasis.

[58]  J. Miletich,et al.  Platelets secrete a coagulation inhibitor functionally and antigenically similar to the lipoprotein associated coagulation inhibitor , 1988 .

[59]  J. Miletich,et al.  Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. , 1988, The Journal of biological chemistry.

[60]  D. Stern,et al.  Modulation of endothelial cell hemostatic properties by tumor necrosis factor , 1986, The Journal of experimental medicine.

[61]  R. Cotran,et al.  Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells , 1984, The Journal of experimental medicine.

[62]  N. Semeraro,et al.  Cultured human endothelial cells generate tissue factor in response to endotoxin. , 1983, The Journal of clinical investigation.

[63]  F. Rickles,et al.  Mononuclear cell tissue factor: cell of origin and requirements for activation , 1979 .

[64]  M. Stemerman,et al.  Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts , 1977 .

[65]  D. Fass,et al.  Tests of hemostasis in swine: normal values and values in pigs affected with von Willebrand's disease. , 1973, American journal of veterinary research.

[66]  T. van der Poll,et al.  Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. , 1994, The Journal of clinical investigation.

[67]  J. Platt,et al.  Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. , 1992, The American journal of pathology.

[68]  J. Platt,et al.  Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival. , 1992, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[69]  D. Cooper,et al.  Experimental Xenotransplantation in Nonhuman Primates Using Distantly Related Donor Species , 1991 .

[70]  F. Taylor,et al.  Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. , 1991, Circulatory shock.

[71]  Y. Nemerson.  Tissue factor and hemostasis. , 1988, Blood.

[72]  C. Esmon,et al.  Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. , 1987, The Journal of clinical investigation.