Download PDF
Thromb Haemost 1998; 79(02): 362-370
DOI: 10.1055/s-0037-1614993
Letters to the Editor
Schattauer GmbH

Modulation of Pro- and Antifibrinolytic Properties of Human Peritoneal Mesothelial Cells by Transforming Growth Factor β1 (TGF- β1), Tumor Necrosis Factor α (TNF-α) and Interleukin β1 (IL-1β)

Lothar Tietze
1   From the Institute of Pathology, Aachen, Germany
,
Anne Elbrecht
1   From the Institute of Pathology, Aachen, Germany
,
Carsten Schauerte
1   From the Institute of Pathology, Aachen, Germany
,
Bernd Klosterhalfen
1   From the Institute of Pathology, Aachen, Germany
,
Baffour Amo-Takyi
1   From the Institute of Pathology, Aachen, Germany
,
Johanna Gehlen
1   From the Institute of Pathology, Aachen, Germany
,
Gerd Winkeltau
2   From the Department of Surgery, the University of Technology, Aachen, Germany
,
Christian Mittermayer
1   From the Institute of Pathology, Aachen, Germany
,
Stefan Handt
1   From the Institute of Pathology, Aachen, Germany
› Author Affiliations
Further Information

Publication History

Received 07 February 1997

Accepted after resubmission 25 September 1997

Publication Date:
08 December 2017 (online)

    Permissions and Reprints

Summary

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF- β1) and interleukin 1β (IL-1β) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-β1, TNF-α and IL-1β induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.

 

  • References

  • 1 Kovacs EJ. Fibrogenic cytokines: The role of immune mediators in the development of scar tissue. Immunol Today 1991; 12: 17.
    CrossrefPubMedGoogle Scholar
  • 2 Fotev Z, Whitaker D, Papadimitriou JM. Role of macrophages in mesothelial healing. J Pathol 1987; 151: 209-19.
    CrossrefPubMedGoogle Scholar
  • 3 Whithaker D, Papadimitriou JM. Mesothelial healing: Morphological and kinetic investigations. J Pathol 1985; 145: 159-75.
    CrossrefPubMedGoogle Scholar
  • 4 Ellis M, Harrison W, Hugh TB. The healing of peritoneum under normal and pathological conditions. Br J Surg 1965; 52: 471-6.
    CrossrefPubMedGoogle Scholar
  • 5 Dobbie JW, Lloyd JK. Mesothelium secretes lamellar bodies in a similar manner to type II pneumocyte secretion of surfactant. Perit Dial Int 1989; 9: 215-9.
    PubMedGoogle Scholar
  • 6 Hills BA, Butler BD, Barrow RE. Boundary lubrication imparted by pleural surfactants and their identification. J Appl Physiol 1982; 53: 463.
    CrossrefPubMedGoogle Scholar
  • 7 Lanfrancone L, Boraschi D, Ghiara P, Falini B, Grignani F, Peri G, Mantovani A, Pelicci PG. Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor CSF, granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to growth by IL-1. Blood 1992; 80: 2835-42.
    PubMedGoogle Scholar
  • 8 Topley N, Jörres A, Luttmann W, Petersen MM, Lang MJ, Thierauch KH, Müller C, Coles GA, Davies M, Williams JD. Human mesothelial cells synthesize interleukin-6: Induction by IL-1 and TNF-. Kidney Int 1993; 43: 226-33.
    CrossrefPubMedGoogle Scholar
  • 9 Topley N, Petersen MM, Mackenzie R, Neubauer A, Stylianou E, Kaever V, Davies M, Coles G, Jrries A, Williams JD. Human peritoneal mesothelial cell prostaglandin synthesis: Induction of cyclooxygenase mRNA by peritoneal macrophage derived cytokines. Kidney Int 1994; 44: 900-9.
    PubMedGoogle Scholar
  • 10 Topley N, Brown Z, Jörres A, Westwick J, Coles G, Davies M, Williams JD. Human peritoneal mesothelial cells synthezise IL-8: synergistic induction by interleukin-1 and tumour necrosis factor alpha. Am J Pathol 1993; 42: 1876-86.
    PubMedGoogle Scholar
  • 11 Offner FA, Feichtinger H, Stadlmann S, Obrist P, Marth C, Klingler P, Grage B, Schmahl M, Knabbe C. Transforming growth factor- synthesis by human peritoneal mesothelial cells. Am J Pathol 1996; 148: 1679-87.
    PubMedGoogle Scholar
  • 12 Jonjic N, Peri G, Bernasconi S, Sciacca FL, Colotta F, Pellici P, Lanfran-cone L, Mantovani A. Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells. J Exp Med 1992; 176: 1165-74.
    CrossrefPubMedGoogle Scholar
  • 13 Davilla RM, Crouch E. Role of mesothelial and submesothelial stromal cells in matrix remodelling following pleural injury. Am J Pathol 1993; 142: 547-55.
    PubMedGoogle Scholar
  • 14 Hinsbergh VWM, Kooistra T, Scheffer AA, van Bockel JH, van Muijen GNP. Characterization and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells. Blood 1990; 75: 1490-97.
    PubMedGoogle Scholar
  • 15 Schleef RR, Loskutoff DJ. Fibrinolytic system of vascular endothelial cells. Haemostasis 1988; 18: 328-41.
    PubMedGoogle Scholar
  • 16 Gervin AS, Puckett CL, Silver D. Serosal hypofibrinolysis, a cause of postoperative abdominal adhesions. Am J Surg 1973; 125: 80-8.
    CrossrefPubMedGoogle Scholar
  • 17 Buckmann RF, Woods M, Sargent L, Gervin AS. A unifying pathogenetic mechanism in the etiology of intraperitoneal adhesions. J Surg Res 1976; 20: 1-5.
    CrossrefPubMedGoogle Scholar
  • 18 Thompson JN, Paterson-Brown S, Harbourne T, Whawell SA, Kalodiki E, Dudley HAF. Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br J Surg 1989; 76: 382-4.
    CrossrefPubMedGoogle Scholar
  • 19 Whawell SA, Scott-Coombes DM, Vipond MN, Tebbutt SJ, Thompson JN. Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells. Br J Surg 1994; 81: 214-6.
    CrossrefPubMedGoogle Scholar
  • 20 Vipond MN, Whawell SA, Thompson JN, Dudley HAF. Peritoneal fibrinolytic activity and intraabdominal adhesions. Lancet 1990; 335: 1120-2.
    CrossrefPubMedGoogle Scholar
  • 21 Kaidi AA, Nazzai M, Gurchumelidze T, Azhar Ali M, Dawe EJ, Silva YJ. Preoperative administration of antibodies against tumor necrosis factor (TNF- ) and interleukin-1 (IL-1) and their impact on peritoneal adhesion formation. Am Surg 1995; 61: 569-72.
    PubMedGoogle Scholar
  • 22 Kaidi AA, Gurchumelidze T, Nazzal M, Figert P, Vanterpool C, Silva Y. Tumor necrosis factor-alpha: a marker for peritoneal adhesion formation. J Surg Res 1995; 58: 516-8.
    CrossrefPubMedGoogle Scholar
  • 23 Chegini N, Gold LI, Williams RS, Masterson BJ. Localisation of transforming growth factor beta isoforms TGF- 1, TGF- 2, and TGF- 3 in the surgically induced pelvic adhesions in the rat. Obstet Gynecol 1994; 83: 449-54.
    PubMedGoogle Scholar
  • 24 Williams RS, Rossi AM, Chegini N, Schultz G. Effect of transforming growth factor on postoperative adhesion formation and intact peritoneum. J Surg Res 1992; 52: 65-70.
    CrossrefPubMedGoogle Scholar
  • 25 Westerhausen DR, Hopkins WE, Billadello JJ. Multiple transforming growth factor beta inducible elements regulate expression of the plasminogen activator inhibitor type 1 gene in HepG2 cells. J Biol Chem 1991; 266: 1092-100.
    PubMedGoogle Scholar
  • 26 Laiho M, Saksela O, Keski-Oja J. Transforming growth factor- induction of type-1 plasminogen activator inhibitor. J Biol Chem 1987; 262: 17467-74.
    PubMedGoogle Scholar
  • 27 Hakkert BC, Rentenaar JM, van Mourik JA. Monocytes enhance the bidirectional release of type 1 plasminogen activator inhibitor by endothelial cells. Blood 1990; 76: 2272-8.
    PubMedGoogle Scholar
  • 28 Fujji S, Hopkins WE, Sobel BE. Mechanisms contributing to increased synthesis of plasminogen activator inhibitor type 1 in endothelial cells by constituents of platelets and their implications for thrombolysis. Circulation 1991; 83: 654-1.
    PubMedGoogle Scholar
  • 29 De Boer JP, Abbink JJ, Brouwer MC, Meijer C, Roem D, Voorn GP, Lambers JW, van Mourik JA, Hack CE. PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines. Evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Idell S, Zwieb C, Kumar A, Koenig KB, Johnson AR. Pathways of fibrin turnover of human pleural mesothelial cells in vitro. Am J Respir Cell Mol Biol 1992; 7: 414-26.
    CrossrefPubMedGoogle Scholar
  • 31 Braaten JV, Jerome WG, Hantgan RR. Uncoupling fibrin from integrin receptors hastens at the platelet-fibrin interface. Blood 1994; 83: 982-93.
    PubMedGoogle Scholar
  • 32 Ranby M, Nguyen G, Scarabin PY, Samama M. Immunoreactivity of tissue type plasminogen activator and its inhibitor complexes: Biochemical and multicenter validation of a two site immunosorbent assay. Thromb Haemost 1989; 61: 409-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Declerck PJ, Collen D. Measurement of plasminogen activator inhibitor 1 (PAI-1) in plasma with various monoclonal antibody-based enzyme-linked immunosorbent assays. Thromb Res Suppl 1990; 10: 3-9.
    PubMedGoogle Scholar
  • 34 Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennet WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D. Cloning and expression of human tissue type plasminogen activator cDNA in E. coli. Nature 1983; 301: 214-21.
    CrossrefPubMedGoogle Scholar
  • 35 Ginsburg D, Zeheb R, Yang AY, Rafferty UM, Adreasen PA, Nielsen L, Dano K, Lebo RV, Gelehrter TD. cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest 1986; 78: 1673-80.
    CrossrefPubMedGoogle Scholar
  • 36 Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T. Molecular structure of the human cytoplasmic -actin gene: Interspecies homology of sequences in the introns. Proc Natl Acad Sci USA 1985; 82: 6133-7.
    CrossrefPubMedGoogle Scholar
  • 37 Handt S, Jerome WG, Tietze L, Hantgan RR. Plasminogen activator inhibitor-1 secretion by endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance. Blood 1996; 87: 4204-13.
    PubMedGoogle Scholar
  • 38 Handt S, Jerome WG, Braaten JV, Lewis JC, Kirkpatrick CJ, Hantgan RR. PAI-1 released from cultured endothelial cells delays fibrinolysis and is incorporated into the developing fibrin clot. Fibrinolysis 1994; 8: 104-12.
    PubMedGoogle Scholar
  • 39 Madison EL, Goldsmith EJ, Gerard RD, Gething MJ, Sambrook JF, BasselDuby RS. Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor type 1. Procl Natl Acad Sci USA 1990; 87: 3530.
    CrossrefPubMedGoogle Scholar
  • 40 Menzies D, Ellis H. Intraabdominal adhesion formation and their prevention by topical tissue plasminogen activator. J R Soc 1989; 82: 534-5.
    PubMedGoogle Scholar
  • 41 Orita H, Fukasawa M, Girgis W, diZerga GS. Inhibition of postsurgical adhesions in a standard rabbit model: intraperitoneal treatment with tissue type plasminogen activator. Int J Fertil 1991; 36: 172-7.
    PubMedGoogle Scholar
  • 42 Whawell SA, Wang Y, Fleming KA, Thompson EM, Thompson JN. Localisation of plasminogen activator inhibitor-1 production in inflamed appendix by in situ mRNA hybridisation. J Pathol 1993; 169: 67-71.
    CrossrefPubMedGoogle Scholar
  • 43 Whawell SA, Thompson EM, Fleming KA, Thompson JN. Plasminogen activator inhibitor 2 expression in inflamed appendix. Histopathology 1995; 27: 75-8.
    CrossrefPubMedGoogle Scholar
  • 44 Speiser W, Anders E, Binder BR, Müller-Berghaus G. Clot lysis mediated by cultured human microvascular endothelial cells. Thromb Haemostas 1987; 463-7.
    PubMedGoogle Scholar
  • 45 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-9.
    PubMedGoogle Scholar
  • 46 Wun Tc, Capuano A. Initiation and regulation of fibrinolysis in human plasma at the plasminogen activator level. Blood 1987; 69: 1354-62.
    PubMedGoogle Scholar
  • 47 Hajjar KA, Hamek NM, Harpel PC, Nachman RL. Binding of tissue plasminogen activator to cultured human endothelial cells. J Clin Invest 1987; 80: 1712-9.
    CrossrefPubMedGoogle Scholar
  • 48 Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator: Identity with annexin II. J Biol Chem 1994; 269: 21191-7.
    PubMedGoogle Scholar
  • 49 Wagner OF, de Vries C, Hohmann C, Veermann H, Pannekoek H. Interaction between plasminogen activator Type 1 bound to fibrin and either tissue-type plasminogen activator or urokinase-type plasminogen activator. J Clin Invest 1989; 84: 647-55.
    CrossrefPubMedGoogle Scholar
  • 50 van Meijer M, Pannekoek H. Structure of plasminogen activator 1 and its function in fibrinolysis: an update. Fibrinolysis 1995; 9: 263-76.
    PubMedGoogle Scholar
  • 51 Kruithof EKO, Baker MS, Bunn CL. Biological and clinical aspects of plasminogen activator inhibitor type 2. Blood 1995; 86: 4007-23.
    PubMedGoogle Scholar