Tissue factor expression demonstrates severe sinusoidal endothelial cell damage during rejection after living-donor liver transplantation
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Since it is well known that endothelial cells may be important targets during rejection after living-donor liver transplantation, in this study we investigated liver sinusoidal endothelial cell (SEC) damage during rejection by focusing on thrombomodulin (TM) and hyaluronic acid (HA) as plasma markers of SEC damage. We also examined tissue factor (TF) expression in SECs, because damage to endothelial cells leads to immediate activation of the coagulation system, with the damage being triggered mainly by TF.
Living-donor liver transplantation was performed at Mie University Hospital between March 2002 and December 2007; there were 8 patients with rejection (4 with acute cellular rejection and 4 with chronic rejection) and 32 patients without rejection. Liver biopsy tissue was immunostained with an anti-TF antibody, and assessed for SEC damage. In addition, total RNA was extracted from liver biopsy tissue and tested for TF mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR).
The plasma TM level was significantly higher in the rejection group than in the non-rejection group. TF expression was observed in SECs, in infiltrating inflammatory cells, and in the vascular endothelium in the rejection group. TF mRNA expression was significantly higher in the rejection group than in the non-rejection group.
We demonstrated that TF expression revealed severe SEC damage in grafted liver during both acute cellular rejection and chronic rejection.
- Tsamandas AC, Jain AB, Felekouras ES, et al. Central venulitis in the allograft liver. Transplantation. 1997;64:252–7. CrossRef
- Wiesner RH, Ludwig J, Hoek B, et al. Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. Hepatology. 1991;14:721–9. CrossRef
- Adams DH, Wang L, Hubscher SG, et al. Hepatic endothelial cells. Target in liver allograft rejection? Transplantation. 1989;47:479–82. CrossRef
- Mor Y, Solomon H, Gibbs JF, et al. Acute cellular rejection following liver transplantation: clinical pathologic features and effect on outcome. Semin Liver Dis. 1992;12:28–40. CrossRef
- Yamaguchi Y, Ichiguchi O, Matsumura F, et al. Enhanced expression of cytokine-induced neutrophil chemoattractant in rat hepatic allografts during acute rejection. Hepatology. 1997;26:1546–52. CrossRef
- Colucci M, Balconi G, Lorenzet R, et al. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest. 1983;71:1893–6. CrossRef
- Maring JK, Klompmaker IJ, Zwaveling JH, et al. Endotoxins and cytokines during liver transplantation: changes in plasma levels and effects on clinical outcome. Liver Transpl. 2000;6:480–8. CrossRef
- Bloem LJ, Chen L, Konigsberg WH, et al. Serum stimulation of quiescent human fibroblasts induces the synthesis of tissue factor mRNA followed by the appearance of tissue factor antigen and procoagulant activity. J Cell Physiol. 1989;139:418–23. CrossRef
- Peppelenbosch MP, Versteeg HH. Cell biology of tissue factor, an unusual member of the cytokine receptor family. Trends Cardiovasc Med. 2001;11:335–9. CrossRef
- Sido B, Datsis K, Mehrabi A, et al. Soluble thrombomodulin—a marker of reperfusion injury after orthotopic liver transplantation. Transplantation. 1995;60:462–6. CrossRef
- Suehiro T, Boros P, Sheiner P, et al. Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation. Liver. 1997;17:224–9.
- Itasaka H, Suehiro T, Wakiyama S, et al. Significance of hyaluronic acid for evaluation of hepatic endothelial cell damage after cold preservation/reperfusion. J Surg Res. 1995;59:589–95. CrossRef
- Demetris AJ, Batts KB, Dhillon AP, et al. Banff schema for grading liver allograft rejection: an international conference document. Hepatology. 1997;25:658–63. CrossRef
- An international panel update of the international Banff schema for liver allograft rejection. Working recommendation for the histopathologic staging and reporting of chronic rejection. Hepatology. 2000;31:792–9. CrossRef
- Higure A, Okamoto K, Hirata K, et al. Macrophages and neutrophils infiltrating into the liver are responsible for tissue factor expression in a rabbit model of acute obstructive cholangitis. Thromb Haemost. 1996;75:791–5.
- Akahane K, Okamoto K, Kikuchi M, et al. Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats. Surgery. 2001;130:809–18. CrossRef
- Pötgens AJ, Lubsen NH, Altena G, et al. Measurement of tissue factor messenger RNA levels in human endothelial cells by a quantitative RT-PCR assay. Thromb Haemost. 1994;71:208–13.
- Chomezynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate–phenol–chloroform extraction. Anal Biochem. 1987;262:611–6.
- Bishop GA, Rokahr KL, Napoli J, et al. Intragraft cytokine mRNA levels in human liver allograft rejection analyzed by reverse transcription and semiquantitative polymerase chain reaction amplification. Transplant Immunol. 1993;1:253–61. CrossRef
- Esmon CT. The role of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem. 1989;264:4743–6.
- Tacke F, Schoffski P, Trautwein C, Manns MP, Ganser A, von Depka M. Tissue factor and thrombomodulin levels are correlated with stage of cirrhosis in patients with liver disease. Blood Coagul Fibrinolysis. 2001;12(7):539–45. CrossRef
- Iino S, Abeyama K, Kawahara KI, Aikou T, Maruyama I. Thrombomodulin expression on Langerhans’ islet: can endogenous ‘anticoagulant on demand’ overcome detrimental thrombotic complications in clinical islet transplantation? J Thromb Haemost. 2004;2:833–4. CrossRef
- Eng HL, Chen YS, Jawan B, et al. Soluble thrombomodulin antigen as a marker for endothelial damage during liver transplantation. Transplant Proc. 2000;32(7):2273–5. CrossRef
- Esmon CT. Coagulation inhibitors in inflammation. Biochem Soc Trans. 2005;33:401–5. CrossRef
- Nakamura S, Imamura T, Okamoto K. Tissue factor in neutrophils: yes. J Thromb Haemost. 2004;2:214–7. CrossRef
- Moberg L, Johansson H, Lukinius A, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002;360:2039–45. CrossRef
- Beuneu C, Vosters O, Movahedi B, et al. Human pancreatic duct cells exert tissue factor-dependent procoagulant activity. Relevance to islet transplantation. Diabetes. 2004;53:1407–11. CrossRef
- Iwata M. Pathophysiology of dogs after 84% hepatectomy with emphasis on prostaglandin metabolites and the effect of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analog. Surg Today. 1994;24:1056–67. CrossRef
- Kuroda H, Kawarada Y, Das BC, et al. Ultrastructual study of the remnant liver after extensive hepatectomy in dogs; especially morphological alterations of sinusoidal endothelial cells. Hepatogastroenterology. 2000;47:450–4.
- Tissue factor expression demonstrates severe sinusoidal endothelial cell damage during rejection after living-donor liver transplantation
Journal of Hepato-Biliary-Pancreatic Surgery
Volume 16, Issue 4 , pp 513-520
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Tissue factor
- Sinusoidal endothelial cell
- Living-donor liver transplantation
- Hyaluronic acid
- Industry Sectors
- Author Affiliations
- 1. Department of Hepatobiliary Pancreatic and Transplant Surgery, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan
- 2. Department of Pathology, Graduate School of Medicine, Mie University, Tsu, Mie, Japan
- 3. First Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
- 4. Department of Hepatobiliary Pancreatic and Transplantation Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan