Differential expression of tissue factor mRNA and protein expression in murine sepsis

Summary

Tissue factor (TF) is a transmembrane protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validateda rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPSmediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however, TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pronflammatory gene expression upon interaction with factor VIIa.

Keywords

Tissue factor - coagulation - sepsis - inflammation - granulocytes

• References

• 1 Nemerson Y. The reaction between bovine brain tissue factor and factors VII and X. Biochemistry 1966; 05: 601-8.
• 2 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; 134: 1087-97.
• 3 Maynard JR, Dreyer BE, Stemerman MB. et al. Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts. Blood 1977; 50: 387-96.
• 4 Taubman MB, Marmur JD, Rosenfield CL. et al. Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells Role of Ca2+ mobilization and protein kinase C activation. J Clin Invest 1993; 91: 547-52.
• 5 Lyberg T, Galdal KS, Evensen SA. et al. Cellular cooperation in endothelial cell thromboplastin synthesis. Br J Haematol 1983; 53: 85-95.
• 6 Bevilacqua MP, Pober JS, Majeau GR. et al. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618-23.
• 7 Stern D, Nawroth P, Handley D. et al. An endothelial cell-dependent pathway of coagulation. Proc Natl Acad Sci US A 1985; 82: 2523-7.
• 8 Rambaldi A, Alessio G, Casali B. et al. Induction of monocyte-macrophage procoagulant activity by transformed cell lines. J Immunol 1986; 136: 3848-55.
• 9 Almdahl SM, Osterud B. Experimental gramnegative septicemia: thromboplastin generation in mononuclear phagocytes from different anatomical sites. Thromb Res 1987; 47: 37-46.
• 10 Lerner RG, Goldstein R, Cummings G. Endotoxin induced disseminated intravascular clotting: evidence that it is mediated by neutrophil production of tissue factor. Thromb Res 1977; 11: 253-61.
• 11 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.
• 12 Todoroki H, Nakamura S, Higure A. et al. Neutrophils express tissue factor in a monkey model of sepsis. Surgery 2000; 127: 209-16.
• 13 Todoroki H, Higure A, Okamoto K. et al. Possible role of platelet-activating factor in the in vivo expression of tissue factor in neutrophils. J Surg Res 1998; 80: 149-55.
• 14 Giesen PL, Rauch U, Bohrmann B. et al. Bloodborne tissue factor: another view of thrombosis. Proc Natl Acad Sci US A 1999; 96: 2311-5.
• 15 Osterud B. Tissue factor in neutrophils: no. J Thromb Haemost 2004; 02: 218-20.
• 16 Drake TA, Cheng J, Chang A. et al. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142: 1458-70.
• 17 Mackman N, Sawdey MS, Keeton MR. et al. Murine tissue factor gene expression in vivo Tissue and cell specificity and regulation by lipopolysaccharide. Am J Pathol 1993; 143: 76-84.
• 18 Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 1996; 97: 2440-51.
• 19 Erlich J, Fearns C, Mathison J. et al. Lipopolysaccharide induction of tissue factor expression in rabbits. Infect Immun 1999; 67: 2540-6.
• 20 Taylor Jr FB, Chang A, Ruf W, Lethal E. et al. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-34.
• 21 Levi M, ten Cate H, Bauer KA. et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-20.
• 22 Creasey AA, Chang AC, Feigen L. et al. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-60.
• 23 Biemond BJ, Levi M, ten Cate H. et al. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa. Thromb Haemost 1995; 73: 223-30.
• 24 Creasey AA, Reinhart K. Tissue factor pathway inhibitor activity in severe sepsis. Crit Care Med 2001; 29: S126-9.
• 25 Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001; 86: 51-6.
• 26 de Jonge E, van der Poll T, Kesecioglu J. et al. Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience. Semin Thromb Hemost 2001; 27: 667-74.
• 27 Carson SD. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane. Blood Coagul Fibrinolysis 1996; 07: 303-13.
• 28 Bach RR, Moldow CF. Mechanism of tissue factor activation on HL-60 cells. Blood 1997; 89: 3270-6.
• 29 Hartzell S, Ryder K, Lanahan A. et al. A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor. Mol Cell Biol 1989; 09: 2567-73.
• 30 de Koster HS, Amons R, Benckhuijsen WE. et al. The use of dedicated peptide libraries permits the discovery of high affinity binding peptides. J Immunol Methods 1995; 187: 179-88.
• 31 Emeis JJ, Lindeman J, Nieuwenhuizen W. Immunoenzyme histochemical localization of fibrin degradation products in tissues. Am J Pathol 1981; 103: 337-44.
• 32 Petersen LC, Norby PL, Branner S. et al. Characterization of recombinant murine factor VIIa and recombinant murine tissue factor: a human-murine species compatibility study. Thromb Res 2005; 116: 75-85.
• 33 Luther T, Flossel C, Mackman N. et al. Tissue factor expression during human and mouse development. Am J Pathol 1996; 149: 101-13.
• 34 Tohgi H, Utsugisawa K, Yoshimura M. et al. Local variation in expression of proand antithrombotic factors in vascular endothelium of human autopsy brain. Acta Neuropathol (Berl) 1999; 98: 111-8.
• 35 Fareed J, Callas DD, Hoppensteadt D. et al. Tissue factor antigen levels in various biological fluids. Blood Coagul Fibrinolysis 1995; 06 (Suppl. 01) S32-6.
• 36 Lwaleed BA, Bass PS, Francis JL. Urinary tissue factor: a potential marker of disease. J Pathol 1999; 188: 3-8.
• 37 Hammerschmidt DE, Weaver LJ, Hudson LD. et al. Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome Pathophysiological relevance and possible prognostic value. Lancet 1980; 01: 947-9.
• 38 Bell WR. The fibrinolytic system in neoplasia. Semin Thromb Hemost 1996; 22: 459-78.
• 39 Hair GA, Padula S, Zeff R. et al. Tissue factor expression in human leukemic cells. Leuk Res 1996; 20: 1-11.
• 40 Osterud B, Rao LV, Olsen JO. Induction of tissue factor expression in whole blood: lack of evidence for the presence of tissue factor expression in granulocytes. Thromb Haemost 2000; 83: 861-7.
• 41 Riewald M, Ruf W. Orchestration of coagulation protease signaling by tissue factor. Trends Cardiovasc Med 2002; 12: 149-54.