Thromb Haemost 1988; 59(03): 392-395
DOI: 10.1055/s-0038-1647502
Original Article
Schattauer GmbH Stuttgart

Evidence for a Discrete Binding Protein of Plasminogen Activator Inhibitor in Plasma

Björn Wiman
The Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden
,
Tomas Lindahl
The Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden
,
Åsa Almqvist
The Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Received 24 September 1987

Accepted after revision 18 January 1988

Publication Date:
29 June 2018 (online)

Summary

Gel-filtration experiments of mixtures of functionally active and inactive forms of plasminogen activator inhibitor (PAI) with human plasma or bovine serum albumin have provided evidence for the existence of a discrete binding protein of PAI in plasma. Most likely it is a glycoprotein with a molecular weight of approximately 150,000. The data suggest that it forms a very stable complex with functionally active forms of PAI, but not with the inactive or “latent” PAI. However, the PAI activity seems not to be significantly altered by the interaction with the binding protein. Assuming that a stoichiometric complex is formed, titration experiments suggest that a pool of normal human plasma contains about 40–50 mg of PAI-binding protein liter.

 
  • References

  • 1 Chmielewska J, Rånby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
  • 2 Kruithof EK O, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-913
  • 3 Verheijen JH, Chang GTG, 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
  • 4 Thorsen S, Philips M. Isolation of tissue-type plasminogen activator inhibitor complexes from human plasma. Biochim Biophys Acta 1984; 802: 111-118
  • 5 Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci 1983; 80: 2956-2960
  • 6 Emeis JJ, van Hinsberg VWM, Verheijen JH, Wijngaards F. Inhibition of tissue-type plasminogen activator by conditioned medium from cultured human and porcine vascular endothelial cells. Biochem Biophys Res Commun 1983; 110: 392-398
  • 7 Laug WE. Vascular smooth cells inhibit the plasminogen activators secreted by endothelial cells. Thromb Haemostas 1985; 53: 165-169
  • 8 Sprengers ED, Princen HMG, Kooistra T, van Hinsbergh VWM. Inhibition of plasminogen activator by conditioned medium of human hepatocytes and hepatoma cell line Hep G2. J Lab Clin Med 1985; 105: 751-758
  • 9 Ny T, Sawdey M, Lawrence D, Millan JL, Loskutoff DJ. Cloning and sequence of a cDNA coding for the human beta-migrating endothelialcell-type plasminogen activator inhibitor. Proc Natl Acad Sci 1986; 83: 6776-6780
  • 10 Pannekoek H, Veerman H, Lambers H, Diergaarde P, Verweij CL, van Zonneveld A-J, van Mourik JA. Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family. EMBO J 1986; 5: 2539-2544
  • 11 Wiman B, Chmielewska J, Rånby M. Inactivation of tissue plasminogen activator in plasma: demonstration of a complex with a new rapid inhibitor. J Biol Chem 1984; 259: 3644-3647
  • 12 Andreasen PA, Nielsen LS, Kristensen P, Grøndahl-Hansen J, Skriver L, Danø K. Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase-type plasminogen activator, but not its proenzyme. J Biol Chem 1986; 261: 7644-7651
  • 13 Chmielewska J, Carlsson T, Urdén G, Wiman B. On the relationship between different molecular forms of the fast inhibitor of tissue plasminogen activator. Fibrinolysis 1987; 1: 67-73
  • 14 Sprengers ED, van Hinsbergh VWM, Jansen BG. The active and inactive plasminogen activator inhibitor from human endothelial cell conditioned medium are immunologically and functionally related to each other. Biochim Biophys Acta 1986; 883: 233-241
  • 15 Hekman CM, Loskutoff DJ. Endothelial cells produce a latent inhibitor or plasminogen activators than can be activated by denaturants. J Biol Chem 1985; 260: 11581-11587
  • 16 Urdén G, Hamsten A, Wiman B. Comparison of plasminogen activator inhibitor activity and antigen in plasma samples. Clin Chim Acta 1987; 169: 189-196
  • 17 Chmielewska J, Wiman B. Determination of tissue plasminogen activator and its “fast” inhibitor in plasma. Clin Chem 1986; 32: 482-485