Download PDF
Thromb Haemost 1993; 69(02): 135-140
DOI: 10.1055/s-0038-1651569
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

Cytokine Regulation of the Synthesis of Plasminogen Activator Inhibitor-2 by Human Vascular Endothelial Cells

Comparison with Plasminogen Activator Inhibitor-1 Synthesis
Hans Zoellner
1   The Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville
,
Johann Wojta
2   The Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Vic., Australia
,
Marisa Gallicchio
2   The Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Vic., Australia
,
Katherine McGrath
2   The Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Vic., Australia
,
John A Hamilton
1   The Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville
› Author Affiliations
Further Information

Publication History

Received 04 May 1992

Accepted after revision 28 September 1992

Publication Date:
03 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Plasminogen activators are inhibited by plasminogen activator inhibitors-1 (PAI-1) and -2 (PAI-2). We describe the synthesis of PAI-2 by human vascular endothelial cells (EC) cultured from umbilical vein, saphenous vein and foreskin microvasculature in response to interleukin-1α (IL־1α) and tumour necrosis factor α (TNFα) and compare it with that of PAI-1. Both PAI-2 and PAI-1 were quantitated by ELIS As. PAI-2 was cell-associated while PAI-1 was secreted by EC. IL-lα and TNFα increased the synthesis of PAI-2 and PAI-1 by EC in a dose-dependent manner. IL-1α was a stronger stimulus for PAI-2 synthesis than TNFα, while both cytokines were equally effective for PAI-1. Northern blot analysis revealed similar changes in mRNA levels to those in antigen levels. PAI-2 synthesis by cytokine-stimulated EC may be important in thrombus formation and inflammation.

 

  • References

  • 1 Danø K, Andreasen PA, Gondahl-Hansen J, Kristensen P, Nielsen LS, Skriver J. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 1985; 44: 139-265
    PubMedSearch in Google Scholar
  • 2 Loskutoff DJ, Curriden SA. The fibrinolytic system of the vessel wall and its role in the control of thrombosis. Ann NY Acad Sci 1990; 598: 238-247
    CrossrefPubMedSearch in Google Scholar
  • 3 Thorsen S, Philips M, Selmer J, Lecander I, Astedt B. Kinetics of inhibition of tissue-type plasminogen activator by plasminogen-activator inhibitor type 1 and type 2. Eur J Biochem 1988; 175: 33-39
    CrossrefPubMedSearch in Google Scholar
  • 4 Kruithof EKO. Plasminogen activator inhibitors - A review. Enzyme 1988; 40: 113-121
    CrossrefPubMedSearch in Google Scholar
  • 5 Laiho M, Keski-Oja J. Growth factors in the regulation of pericellular proteolysis: a review. Cancer Res 1989; 49: 2533-2553
    PubMedSearch in Google Scholar
  • 6 Genton C, Kruithof EKO, Schleuning WD. Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor-2 in high excess over urokinase type plasminogen activator in human 937-lymphoid cells. J Cell Biol 1987; 104: 705-712
    CrossrefPubMedSearch in Google Scholar
  • 7 Wohlwend A, Belin D, Vassalli JD. Plasminogen activator-specific inhibitors produced by human monocytes/macrophages. J Exp Med 1987; 165: 320-339
    CrossrefPubMedSearch in Google Scholar
  • 8 Kumar S, Baglioni C. Protection from tumour necrosis factor mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. J Biol Chem 1991; 266: 20960-20964
    PubMedSearch in Google Scholar
  • 9 Pytel B, Peppel K, Baglioni C. Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumour necrosis factor. J Cell Physiol 1990; 144: 416-422
    CrossrefPubMedSearch in Google Scholar
  • 10 Medcalf RL, Kruithof EKO, Schleuning WD. Plasminogen activator inhibitor 1 and 2 are tumour necrosis factor/cachectin responsive genes. J Exp Med 1988; 168: 751-759
    CrossrefPubMedSearch in Google Scholar
  • 11 Goeken NE, Staggs TS, Ballas ZK. Monocyte suppressor factor is plasminogen activator inhibitor, inhibition of membrane bound but not soluble IL-1. J Immunol 1989; 143: 603-608
    PubMedSearch in Google Scholar
  • 12 Mantovani A, Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 1989; 10: 370-375
    CrossrefPubMedSearch in Google Scholar
  • 13 Van Hinsbergh VWM, Van Den Berg EA, Fiers W, Dooijewaards G. Tumour necrosis factor induces the production of urokinase types plasminogen activator by human endothelial cells. Blood 1990; 75: 1991-1998
    PubMedSearch in Google Scholar
  • 14 Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone MA, Loskutoff DJ. Cytokine activation of vascular endothelium. J Biol Chem 1988; 263: 5797-5803
    PubMedSearch in Google Scholar
  • 15 Van Hinsbergh VWM, Kooistra T, van Den Berg EA, Princen HMG, Fiers W, Emeis JJ. Tumour necrosis factor increases the production of plasminogen activator inhibitor by human endothelial cells in vitro and in rats in vivo. Blood 1988; 72: 1467-1473
    PubMedSearch in Google Scholar
  • 16 Scarpati EM, Sadler JE. Regulation of endothelial cell coagulant properties. J Biol Chem 1989; 34: 20705-20713
    PubMedSearch in Google Scholar
  • 17 Loskutoff DJ, Edington TS. Synthesis of fibrinolytic activator and inhibitor by endothelial cells. Proc Natl Acad Sci 1977; 74: 3903-3907
    CrossrefPubMedSearch in Google Scholar
  • 18 Gimbrone MA, Cotran R, Folkman JJ. Human vascular endothelial cells in culture. J Cell Biol 1974; 60: 673-684
    CrossrefPubMedSearch in Google Scholar
  • 19 Jackson CJ, Garbett PK, Nissen B, Schreiber L. Binding of human endothelium to Ulex europaeus 1-coated dynabeads: application to the isolation of microvascular endothelium. J Cell Sci 1990; 96: 257-263
    PubMedSearch in Google Scholar
  • 20 Maciag T, Hoover GA, Stemerman MB, Wellnstein R. Factors which stimulate the growth of human umbilical vein endothelial cells in vitro. In: Biology of Endothelial Cells. Jaffe EA. (ed) Martinus Nijhoff Publ.; Dordrecht: 1984: 87-96
    Search in Google Scholar
  • 21 Jaffe EA, Hoyer LW, Nachman R. Synthesis of antihemophylic factor antigen by cultured human endothelial cells. J Clin Invest 1980; 52: 2757-2764
    PubMedSearch in Google Scholar
  • 22 Stein O, Stein Y. Bovine aortic endothelial cells display macrophagelike properties towards acetylated 125I-labelled low density lipoprotein. Biochem Biophys Acta 1980; 620: 631-635
    CrossrefPubMedSearch in Google Scholar
  • 23 Jaffe EA, Nachman RL, Becher CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-2756
    CrossrefPubMedSearch in Google Scholar
  • 24 Hamilton JA, Whitty GA, Last KA, Royston K, Burges DR. Interleukin-4 suppresses plasminogen activator inhibitor-2 formation in stimulated human monocytes. Blood. 1992 (in press)
    PubMedSearch in Google Scholar
  • 25 Antalis TM, Clark MA, Barns T, Lehrbach PR, Devine PL, Schevozov G, Goss NH, Stephens RW, Tostoshev P. Cloning and expression of a cDNA coding for a human monocyte-derived plasminogen activator inhibitor. Proc Natl Acad Sci USA 1985; 85: 955-959
    PubMedSearch in Google Scholar
  • 26 Wojta J, Holzer M, Hufnagl P, Christ G, Hoover RL, Binder BR. Hyperthermia stimulates plasminogen activator inhibitor Type 1 expression in human umbilical vein endothelial cells in vitro. Am J Pathol 1991; 139: 911-919
    PubMedSearch in Google Scholar
  • 27 Wagner OF, Binder BR. Purification of an active plasminogen activator inhibitor immunologically related to endothelial type plasminogen activator inhibitor from the conditioned media of a human melanoma cell line. J Biol Chem 1986; 261: 14474-14481
    PubMedSearch in Google Scholar
  • 28 Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribo-nuclease. Biochemistry 1979; 18: 5294-5299
    CrossrefPubMedSearch in Google Scholar
  • 29 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4354
    CrossrefPubMedSearch in Google Scholar
  • 30 Niiya K, Takeuchi T, Kobayashi M, Miyoshi I, Hayashi T, Sakuagawa N. Dexamethasone and phorbol ester, but not cytokines increase the production of plasminogen activator inhibitor types-2 in the PL-21 human promyelocytic leukemia cell line. Thromb Haemostas 1991; 66: 232-238
    PubMedSearch in Google Scholar
  • 31 Michel JB, Quertermous T. Modulation of mRNA levels for urinary-and tissue-type plasminogen activator inhibitors 1 and 2 in human fibroblasts by interleukin 1. J Immunol 1989; 143: 890-895
    PubMedSearch in Google Scholar
  • 32 Emeis J, Koositra 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
    CrossrefPubMedSearch in Google Scholar
  • 33 Schleef RR, Wagner NV, Loskutoff DJ. Detection of both type 1 and type 2 plasminogen activator inhibitor in human cells. J Cell Physiol 1988; 134: 269-274
    CrossrefPubMedSearch in Google Scholar
  • 34 Rånby M, Brändström A. Biological control of tissue plasminogen activator mediated fibrinolysis. Enzyme 1988; 40: 130-143
    CrossrefPubMedSearch in Google Scholar
  • 35 Hansson GK, Jonasson L, Seifert PS, Stemme S. Immune mechanims in atherosclerosis. Atherosclerosis 1989; 9: 567-578
    PubMedSearch in Google Scholar
  • 36 Moore P. Immune mechanisms in the primary and secondary vasculitides. J Neurol Sci 1989; 93: 129-141
    CrossrefPubMedSearch in Google Scholar
  • 37 Anderson JR. The heart. In: Muirs Textbook of Pathology. 12.. Anderson JR. (ed) Edward Arnold (Publ); London: 1985
    Search in Google Scholar
  • 38 Goldblum SE, Henning B, Jay M, Kokichi Y, McClain CJ. Tumour necrosis factor β induced pulmonary endothelial injury. Infect Immun 1989; 57: 1218-1226
    PubMedSearch in Google Scholar
  • 39 Schuger L, Varani J, Marks RM, Kunkel SL, Johnson KL, Ward PA. Cytotoxicity of tumour necrosis factor-β for human umbilical vein endothelial cells. Lab Invest 1989; 61: 62-68
    PubMedSearch in Google Scholar