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Thromb Haemost 1983; 50(04): 888-892
DOI: 10.1055/s-0038-1665336
Original Article
Schattauer GmbH Stuttgart

Glucocorticoids Inhibit Plasminogen Activator Production by Endothelial Cells

Walter E Laug
The Division of Hematology-Oncology, Children’s Hospital of Los Angeles and University of Southern California School of Medicine, Los Angeles, CA, U.S.A.
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Further Information

Publication History

Received 05 May 1983

Accepted 26 October 1983

Publication Date:
18 July 2018 (online)

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Summary

Confluent cultures of bovine aortic endothelial cells (BEC) were found to secrete both tissue type plasminogen activator (t- PA) and urokinase type plasminogen activator (u-PA). Exposure of the cultures to increasing concentrations of dexamethasone resulted in a time and concentration dependent inhibition of cellular and secreted u-PA. Complete inhibition of u-PA production and secretion was found at dexamethasone concentrations of 10-8 molar or higher. Several distinct PA forms with molecular weights ranging from 10,000-20,000 to >200,000 were found in the conditioned medium of untreated BEC cultures. After addition of dexamethasone (10-7 molar) to the culture medium the PAs with molecular weights of 117,000, 58,000,47,000, were absent suggesting that they were u-PAs, whereas the PAs with molecular weights of >200,000 and 75,000 remained unchanged suggesting their t-PA origins. The PAs with lower molecular weights of 35,000, 28,000 and 10,000 to 20,000 were most likely generated from the higher molecular weight forms by limited proteolysis since they were absent when the medium was conditioned in the presence of the protease inhibitor Trasylol.

The two PA types may therefore be independently regulated in BEC.

Keywords

Endothelial cells - Plasminogen activators - Corticosteroids - Inhibition
 

  • References

  • 1 Laug WE, Tokes Z, Benedict WF, Sorgente N. Anchorage independent growth and plasminogen activator production by bovine endothelial cells. J Cell Biol 1980; 84: 281-293
    CrossrefPubMedGoogle Scholar
  • 2 Laug WE. Secretion of plasminogen activators by cultured bovine endothelial cells: Partial purification, characterization and evidence for multiple forms. Thromb Haemostas 1981; 45: 219-224
    PubMedGoogle Scholar
  • 3 Levin EG, Loskutoff DJ. Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators. J Cell Biol 1982; 94: 631-636
    CrossrefPubMedGoogle Scholar
  • 4 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
    PubMedGoogle Scholar
  • 5 Loskutoff DJ, Edgington TS. Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. Proc Natl Acad Sci USA 1977; 74: 3903-3907
    CrossrefPubMedGoogle Scholar
  • 6 Gross JL, Moscatelli D, Jaffe EA, Rifkin DB. Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol 1982; 95: 974-981
    CrossrefPubMedGoogle Scholar
  • 7 Laug WE. Alcohol enhances plasminogen activator secretion by endothelial cells. JAMA 1983; 250: 772-776
    CrossrefPubMedGoogle Scholar
  • 8 Nilson IM. Phenformin and ethylestranol in recurrent thrombosis. In: Progress in chemical fibrinolysis and thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (eds) Raven Press; New York: 1975. 1 1-12
    Google Scholar
  • 9 Rasheed S, Nelson-Rees WA, Toth EM, Arnstein P, Gardner MB. Characterization of a newly derived human sarcoma cell line (HT 1080). Cancer 1974; 33: 1027-1033
    CrossrefPubMedGoogle Scholar
  • 10 Rijken DC, Collen D. Purification and characterization of the plas-minogen activator secreted by human melanoma cells in culture. J Biol Chem 1981; 256: 7035-7041
    PubMedGoogle Scholar
  • 11 McAllister RM, Meluyke J, Finkelstein JF, Adams EC, Gardner MB. Cultivation in vitro of cells derived from a human rhabdomyosar-coma. Cancer 1969; 24: 520-526
    CrossrefPubMedGoogle Scholar
  • 12 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275
    PubMedGoogle Scholar
  • 13 Roblin R, Young PL. Dexamethasone regulation of plasminogen activator in embryonic and tumor derived human cells. Cancer Res 1980; 40: 2706-2713
    PubMedGoogle Scholar
  • 14 Wiinschmann-Henderson B, Astrup T. Inhibition by hydrocortisone of plasminogen activator production in rat tongue organ cultures. Lab Invest 1974; 30: 427-433
    PubMedGoogle Scholar
  • 15 Vassalli JD, Hamilton J, Reich E. Macrophage plasminogen activa-tor: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides. Cell 1976; 8: 271-281
    CrossrefPubMedGoogle Scholar
  • 16 Granelli-Piperno A, Vassalli JD, Reich E. Secretion of plasminogen activator by human polymorphonuclear leukocytes: Modulation by glucocorticoids and other effectors. J Exp Med 1977; 146: 1693-1706
    CrossrefPubMedGoogle Scholar
  • 17 Wigler M, Ford J P, Weinstein IB. Glucocorticoid inhibition of the fibrinolytic activity of tumor cells. In: Proteases and Biological Control. Reich E, Rifkin DB, Shaw E. (eds) pp 849-856 Cold Spring Harbor Laboratory; Cold Spring Harbor, New York: 1975
    Google Scholar
  • 18 Huber K, Kirchheimer J, Binder BR. Rapid isolation of high molecular weight urokinase from native human urine. Thromb Haemostas 1982; 47: 197-202
    PubMedGoogle Scholar
  • 19 Seifert SC, Gelehrter TD. Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells. Proc Natl Acad Sci USA 1978; 75 (12) 6130-6133
    CrossrefPubMedGoogle Scholar
  • 20 Matsuo O, Rijken DC, Collen D. Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus. Nature 1981; 291: 590-591
    CrossrefPubMedGoogle Scholar
  • 21 Weimar W, Stibbe J, Van Seyen AJ, Billian A, De Somer P, Collen D. Specific lysis of an iliofemoral thrombus by administration of extrinsic (tissue-type) plasminogen activator. Lancet 1981; 2: 1018-1020
    PubMedGoogle Scholar