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Thromb Haemost 1988; 59(03): 451-454
DOI: 10.1055/s-0038-1647514
Original Article
Schattauer GmbH Stuttgart

Plasminogen Activator Inhibitor Activity in Bacterial Infection

J A Páramo
The Hematology Service, University Clinic, University of Navarra, Pamplona, Spain
,
F J Fernández Diaz
The Hematology Service, University Clinic, University of Navarra, Pamplona, Spain
,
E Rocha
The Hematology Service, University Clinic, University of Navarra, Pamplona, Spain
› Author Affiliations
Further Information

Publication History

Received 19 November 1987

Accepted after revision 09 February 1988

Publication Date:
29 June 2018 (online)

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Summary

It has been experimentally shown that endotoxin induces a marked increase in the levels of a fast-acting inhibitor of plasminogen activator (PAI). The plasma PAI activity and tissuetype plasminogen activator (t-PA) concentrations were measured in 61 patients with human septicaemia and results were compared with those observed in healthy controls. There was a markedly significant increase of PAI in plasma and platelet extracts of patients with septicaemia as compared to controls (p <0.0001). No correlation between PAI and endotoxin concentration was observed. Fibrin autography of plasma samples confirmed that activator inhibition was associated with the formation of an enzyme-inhibitor complex. t-PA activity was similar in patients and controls, whereas t-PA Ag showed a significant increase in patients (p <0.0001). A significant inverse correlation between t-PA activity and PAI was observed (p <0.05). PAI activity was higher in patients with positive blood cultures (p <0.0001) and gram-negative septicaemia (p <0.0001). There was also a significant increase of PAI levels in patients with disseminated intravascular coagulation (DIC) as compared with patients without DIC (p <0.001). We conclude that there is a marked increase of PAI in patients with sepsis. Increased PAI activity may contribute to the pathogenesis of DIC associated with septicaemia.

Keywords

Plasminogen activator inhibitor - Bacterial infection - Disseminated intravascular coagulation
 

  • References

  • 1 Morrison DC, Ulevitch RJ. The effects of bacterial endotoxins on host mediation systems. A review Am J Pathol 1978; 93: 526-617
    PubMedGoogle Scholar
  • 2 Mizock B. Septic shock. A metabolic perspective Arch Intern Med 1984; 144: 579-585
    CrossrefPubMedGoogle Scholar
  • 3 Loskutoff DJ. The fibrinolytic system of cultured endothelial cells: deciphering the balance between plasminogen activation and inhibition. In: Progress in Fibrinolysis, Vol 7. Davidson JF, Donati MB, Coccheri S. (eds) Churchill Livingstone; Edinburgh: 1985: 15-22
    Google Scholar
  • 4 Nilsson IM, Hedner U, Pandolfi M. Physiology of fibrinolysis. In: Fibrinolysis. Kline DL, Reddy KNN. (eds) CRC Press, Inc.; Boca Raton, FL: 1980: 165-183
    Google Scholar
  • 5 Verheijen JH, Chang GT G, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-395
    PubMedGoogle Scholar
  • 6 Kruithof EK O, Tran-Thang C, Ransijn A, Bachman F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-913
    PubMedGoogle Scholar
  • 7 Wiman B, Chmielewska J, Ranby M. Inactivation of tissue plasminogen activator in plasma. J Biol Chem 1984; 259: 3644-3647
    PubMedGoogle Scholar
  • 8 Thorsen S, Philips M. Isolation of tissue type plasminogen activator inhibitor complexes from human plasma. Biochim Biophys Acta 1984; 802: 111-118
    CrossrefPubMedGoogle Scholar
  • 9 Juhan-Vague I, Moerman B, De Cock F, Aillaud MF, Collen D. Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb Res 1984; 33: 523-530
    CrossrefPubMedGoogle Scholar
  • 10 Erickson LA, Ginsberg MH, Loskutoff DJ. Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. J Clin Invest 1984; 74: 1465-1472
    CrossrefPubMedGoogle Scholar
  • 11 Holmberg L, Lecander I, Persson B, Astedt B. An inhibitor from human placenta specifically binds urokinase and inhibits plasminogen activators released from ovarian carcinoma in tissue culture. Biochim Biophys Acta 1978; 544: 128-137
    CrossrefPubMedGoogle Scholar
  • 12 Dosne AM, Dupuy E, Bodevin E. Production of a fibrinolytic inhibitor by cultured endothelial cells derived from human umbilical vein. Thromb Res 1978; 12: 377-387
    CrossrefPubMedGoogle Scholar
  • 13 Emeis JJ, Van Hinsberg VW M, Verheijen JH, Wijngaards G. Inhibition of tissue-type plasminogen activator by conditium medium from cultured human and porcine vascular endothelial cells. Biochem Biophys Res Commun 1983; 110: 392-398
    CrossrefPubMedGoogle Scholar
  • 14 Levin EG. Latent tissue plasminogen activator produced by human endothelial cells in culture: evidence for an enzyme-inhibitor complex. Proc Natl Acad Sci USA 1983; 80: 6804-6808
    CrossrefPubMedGoogle Scholar
  • 15 Sprengers ED, Verheijen JH, Van Hinsberg VW M, Emeis JJ. Evidence for the presence of two different fibrinolytic inhibitors in human endothelial cells conditioned medium. Biochim Biophys Acta 1984; 801: 163-170
    CrossrefPubMedGoogle Scholar
  • 16 Philips M, Juul A, Thorsen S. Human endothelial cells produce a plasminogen activator inhibitor and a tissue-type plasminogen activator-inhibitor complex. Biochim Biophys Acta 1984; 802: 99-110
    CrossrefPubMedGoogle Scholar
  • 17 Van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (anti-activator) synthesized by endothelial cells. J Biol Chem 1984; 259: 14914-14921
    PubMedGoogle Scholar
  • 18 Sprengers ED, Kluft TC. Plasminogen activator inhibitors. Blood 1987; 69: 381-387
    PubMedGoogle Scholar
  • 19 Colucci M, Páramo JA, Collen D. Generation in plasma of a fast- acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-824
    CrossrefPubMedGoogle Scholar
  • 20 Verheijen JH, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-269
    PubMedGoogle Scholar
  • 21 Páramo JA, Alfaro MJ, Rocha E. Postoperative changes in the plasmatic levels of tissue-type plasminogen activator and its fast-acting inhibitor. Relationship to deep vein thrombosis and influence of prophylaxis Thromb Haemostas 1985; 54: 713-716
    PubMedGoogle Scholar
  • 22 Loskutoff DJ, Mussoni J. Interactions between fibrin and the plasminogen activators produced by cultured endothelial cells. Blood 1983; 62: 62-68
    PubMedGoogle Scholar
  • 23 Wiman B, Ljungberg B, Chmielewska J, Urden G, Blomback M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 1985; 105: 265-270
    PubMedGoogle Scholar
  • 24 Páramo JA, Colucci M, Collen D, Van de Werf F. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br Med J 1985; 291: 573-574
    CrossrefPubMedGoogle Scholar
  • 25 Páramo JA, De Boer A, Colucci M, Jonker JJ C, Collen D. Plasminogen activator inhibitor (PA-inhibitor) in the blood of patients with deep vein thrombosis. Thromb Haemostas 1985; 54: 725
    PubMedGoogle Scholar
  • 26 Crutchley DJ, Conanan LB. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells. J Biol Chem 1986; 261: 154-159
    PubMedGoogle Scholar
  • 27 Emeis JJ, Kooistra T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260-1266
    CrossrefPubMedGoogle Scholar
  • 28 Verheijen JH, Sprengers ED, Emeis JJ, Van Hinsbergh VW M, Chang GT G, Kluft C. Tissue-plasminogen activator inhibition by human endothelial cell conditioned medium. In: Progress in Fibrinolysis, Vol 7. Davidson JF, Donati MB, Coccheri S. (eds) Churchill Livingstone; Edinburgh: 1985: 141-145
    Google Scholar
  • 29 Erickson LA, Hekman CM, Loskutoff DJ. The primary plasminogen-activators inhibitors in endothelial cells, platelets, serum, and plasma are immunologically related. Proc Natl Acad Sci USA 1985; 82: 8710-8714
    CrossrefPubMedGoogle Scholar
  • 30 Philips M, Juul AG, Thorsen S, Selmer J, Zeuthen J. Immunological relationship between the fast-acting plasminogen activator inhibitors from plasma, blood platelets and endothelial cells demonstrated with a monoclonal antibody against an inhibitor from placenta. Thromb Haemostas 1986; 55: 213-217
    PubMedGoogle Scholar
  • 31 Urdén G, Chmielewska J, Carlsson T, Wiman B. Immunological relationship between plasminogen activator inhibitors from different sources. Thromb Haemostas 1987; 57: 29-34
    PubMedGoogle Scholar
  • 32 Sprengers ED, Akkerman JW N, Jansen BG. Blood platelet plasminogen activator inhibitor: two different pools of endothelial cell type plasminogen activator inhibitor in human blood. Thromb Haemostas 1986; 55: 325-329
    PubMedGoogle Scholar
  • 33 Kruithof EK O, Tran-Thang C, Bachmann F. Studies on the release of a plasminogen activator inhibitor by human platelets. Thromb Haemostas 1986; 55: 201-205
    PubMedGoogle Scholar
  • 34 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-1455
    CrossrefPubMedGoogle Scholar
  • 35 Juhan-Vague I, Aillaud MF, De Cock F, Philip-Joet C, Amaud C, Serradimigni A, Collen D. The fast-acting inhibitor of tissue-type plasminogen activator is an acute phase reactant protein. In: Progress in Fibrinolysis, Vol7. Davidson JF, Donati MB, Cocheri S. (eds) Churchill Livingstone; Edinburgh: 1985: 146-149
    Google Scholar
  • 36 Gelerther TD, Sznycer-Laszuk R. Thrombin induction of plasminogen activator-inhibitor in cultured human endothelial cells. J Clin Invest 1986; 77: 165-169
    CrossrefPubMedGoogle Scholar
  • 37 Bevilacqua MP, Schleff RR, Gimbrone Jr MA, Loskutoff DJ. Regulation of the fibrinolytic system of cultured human vascular endothelium by interleukin 1. J Clin Invest 1986; 77: 587-591
    PubMedGoogle Scholar
  • 38 Colucci M, Páramo JA, Collen D. Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fast-acting inhibitor of plasminogen activator in vitro and in vivo. J Lab Clin Med 1986; 108: 53-59
    PubMedGoogle Scholar