Skip to main content

Plasmin-Antiplasmin System

  • Chapter
  • First Online:
Trauma Induced Coagulopathy

Abstract

Plasmin is the key enzyme involved in the dissolution of fibrin. It is produced from plasminogen, which is activated by a plasminogen activator; the two primary activators are tissue-type plasminogen activator (tPA) and urinary-type plasminogen activator (uPA), also called urokinase. The process is regulated by inhibitors, principally plasminogen activator inhibitor 1 (PAI-1), α2-antiplasmin (α2AP) and thrombin-activatable fibrinolysis inhibitor (TAFI). Crucial control is exerted by surfaces, such as fibrin or cells, with plasminogen activation not normally occurring in the circulation. Here we will consider the individual players of the fibrinolytic cascade and their specific locations and potential interactions. Key questions considered are the initiation of fibrinolysis and the most appropriate ways to measure abnormalities in disease situations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gaffney PJ. Fibrin degradation products. A review of structures found in vitro and in vivo. Ann N Y Acad Sci. 2001;936:594–610.

    Article  CAS  PubMed  Google Scholar 

  2. Dudek GA, Kloczewiak M, Budzynski AZ, Latallo ZS, Kopec M. Characterisation and comparison of macromolecular end products of fibrinogen and fibrin proteolysis by plasmin. Biochim Biophys Acta. 1970;214:44–51.

    Article  CAS  PubMed  Google Scholar 

  3. Pizzo SV, Schwartz ML, Hill RL, McKee PA. The effect of plasmin on the subunit structure of human fibrin. J Biol Chem. 1973;248:4574–83.

    CAS  PubMed  Google Scholar 

  4. Francis CW, Marder VJ, Barlow GH. Plasmic degradation of crosslinked fibrin. Characterization of new macromolecular soluble complexes and a model of their structure. J Clin Invest. 1980;66:1033–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin. J Biol Chem. 1999;274:5201–12.

    Article  CAS  PubMed  Google Scholar 

  6. Hedner U. Urinary fibrin/fibrinogen derivatives. Thromb Diath Haemorrh. 1975;34:693–708.

    CAS  PubMed  Google Scholar 

  7. Dardik BN, Shainoff JR. Kinetic characterization of a saturable pathway for rapid clearance of circulating fibrin monomer. Blood. 1985;65:680–8.

    CAS  PubMed  Google Scholar 

  8. Bannach FG, Gutierrez A, Fowler BJ, Bugge TH, Degen JL, Parmer RJ, Miles LA. Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expression. J Biol Chem. 2002;277:38579–88.

    Article  CAS  PubMed  Google Scholar 

  9. Raum D, Marcus D, Alper CA, Levey R, Taylor PD, Starzl TE. Synthesis of human plasminogen by the liver. Science. 1980;208:1036–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Highsmith RF, Kline DL. Kidney: primary source of plasminogen after acute depletion in the cat. Science. 1971;174:141–2.

    Article  CAS  PubMed  Google Scholar 

  11. Twining SS, Wilson PM, Ngamkitidechakul C. Extrahepatic synthesis of plasminogen in the human cornea is up-regulated by interleukins-1alpha and -1beta. Biochem J. 1999;339(Pt 3):705–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang L, Seiffert D, Fowler BJ, Jenkins GR, Thinnes TC, Loskutoff DJ, Parmer RJ, Miles LA. Plasminogen has a broad extrahepatic distribution. Thromb Haemost. 2002;87:493–501.

    CAS  PubMed  Google Scholar 

  13. Schuster V, Mingers AM, Seidenspinner S, Nussgens Z, Pukrop T, Kreth HW. Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood. 1997;90:958–66.

    CAS  PubMed  Google Scholar 

  14. Mangel WF, Lin BH, Ramakrishnan V. Characterization of an extremely large, ligand-induced conformational change in plasminogen. Science. 1990;248:69–73.

    Article  CAS  PubMed  Google Scholar 

  15. Urano T, Chibber BA, Castellino FJ. The reciprocal effects of epsilon-aminohexanoic acid and chloride ion on the activation of human [Glu1]plasminogen by human urokinase. Proc Natl Acad Sci U S A. 1987;84:4031–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sjoholm I. Studies on the conformational changes of plasminogen induced during activation to plasmin and by 6-aminohexanoic acid. Eur J Biochem. 1973;39:471–9.

    Article  CAS  PubMed  Google Scholar 

  17. Castellino FJ. Biochemistry of human plasminogen. Semin Thromb Hemost. 1984;10:18–23.

    Article  CAS  PubMed  Google Scholar 

  18. Plow EF, Doeuvre L, Das R. So many plasminogen receptors: why? J Biomed Biotechnol. 2012;2012:141806.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Miles LA, Castellino FJ, Gong Y. Critical role for conversion of glu-plasminogen to Lys-plasminogen for optimal stimulation of plasminogen activation on cell surfaces. Trends Cardiovasc Med. 2003;13:21–30.

    Article  CAS  PubMed  Google Scholar 

  20. Madison EL. Probing structure-function relationships of tissue-type plasminogen activator by site-specific mutagenesis. Fibrinolysis. 1994;8:221–6.

    Article  CAS  Google Scholar 

  21. Stalder M, Hauert J, Kruithof EK, Bachmann F. Release of vascular plasminogen activator (v-PA) after venous stasis: electrophoretic-zymographic analysis of free and complexed v-PA. Br J Haematol. 1985;61:169–76.

    Article  CAS  PubMed  Google Scholar 

  22. Booth NA, Walker E, Maughan R, Bennett B. Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1. Blood. 1987;69:1600–4.

    CAS  PubMed  Google Scholar 

  23. Tappy L, Hauert J, Bachmann F. Effects of hypoxia and acidosis on vascular plasminogen activator release in the pig ear perfusion system. Thromb Res. 1984;33:117–24.

    Article  CAS  PubMed  Google Scholar 

  24. Vaughan DE. The renin-angiotensin system and fibrinolysis. Am J Cardiol. 1997;79:12–6.

    Article  CAS  PubMed  Google Scholar 

  25. Chandler WL, Levy WC, Stratton JR. The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation. 1995;92:2984–94.

    Article  CAS  PubMed  Google Scholar 

  26. Strickland DK, Ranganathan S. Diverse role of LDL receptor-related protein in the clearance of proteases and in signaling. J Thromb Haemost. 2003;1:1663–70.

    Article  CAS  PubMed  Google Scholar 

  27. van Zonneveld AJ, Veerman H, Pannekoek H. On the interaction of the finger and the kringle-2 domain of tissue-type plasminogen activator with fibrin. Inhibition of kringle-2 binding to fibrin by epsilon-amino caproic acid. J Biol Chem. 1986;261:14214–8.

    PubMed  Google Scholar 

  28. Longstaff C, Thelwell C, Williams SC, Silva MM, Szabo L, Kolev K. The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: kinetic and microscopic studies. Blood. 2011;117:661–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Medved L, Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin. Thromb Haemost. 2003;89:409–19.

    CAS  PubMed  Google Scholar 

  30. Higgins DL, Vehar GA. Interaction of one-chain and two-chain tissue plasminogen activator with intact and plasmin-degraded fibrin. Biochemistry. 1987;26:7786–91.

    Article  CAS  PubMed  Google Scholar 

  31. Ranby M, Bergsdorf N, Nilsson T. Enzymatic properties of the one- and two-chain form of tissue plasminogen activator. Thromb Res. 1982;27:175–83.

    Article  CAS  PubMed  Google Scholar 

  32. Rijken DC, Hoylaerts M, Collen D. Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J Biol Chem. 1982;257:2920–5.

    CAS  PubMed  Google Scholar 

  33. Ranby M. Studies on the kinetics of plasminogen activation by tissue plasminogen activator. Biochim Biophys Acta. 1982;704:461–9.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    CAS  PubMed  Google Scholar 

  35. Geppert AG, Binder BR. Allosteric regulation of tPA-mediated plasminogen activation by a modifier mechanism: evidence for a binding site for plasminogen on the tPA A-chain. Arch Biochem Biophys. 1992;297:205–12.

    Article  CAS  PubMed  Google Scholar 

  36. Norrman B, Wallen P, Ranby M. Fibrinolysis mediated by tissue plasminogen activator. Disclosure of a kinetic transition. Eur J Biochem. 1985;149:193–200.

    Article  CAS  PubMed  Google Scholar 

  37. Suenson E, Lutzen O, Thorsen S. Initial plasmin-degradation of fibrin as the basis of a positive feed-back mechanism in fibrinolysis. Eur J Biochem. 1984;140:513–22.

    Article  CAS  PubMed  Google Scholar 

  38. Harpel PC, Chang TS, Verderber E. Tissue plasminogen activator and urokinase mediate the binding of Glu-plasminogen to plasma fibrin I. Evidence for new binding sites in plasmin-degraded fibrin I. J Biol Chem. 1985;260:4432–40.

    CAS  PubMed  Google Scholar 

  39. Tran-Thang C, Kruithof EK, Atkinson J, Bachmann F. High-affinity binding sites for human Glu-plasminogen unveiled by limited plasmic degradation of human fibrin. Eur J Biochem. 1986;160:599–604.

    Article  CAS  PubMed  Google Scholar 

  40. Rijken DC, Wijngaards G, Zaal-de Jong M, Welbergen J. Purification and partial characterization of plasminogen activator from human uterine tissue. Biochim Biophys Acta. 1979;580:140–53.

    Article  CAS  PubMed  Google Scholar 

  41. de Vries C, Veerman H, Koornneef E, Pannekoek H. Tissue-type plasminogen activator and its substrate Glu-plasminogen share common binding sites in limited plasmin-digested fibrin. J Biol Chem. 1990;265:13547–52.

    PubMed  Google Scholar 

  42. Larsson LI, Skriver L, Nielsen LS, Grondahl-Hansen J, Kristensen P, Dano K. Distribution of urokinase-type plasminogen activator immunoreactivity in the mouse. J Cell Biol. 1984;98:894–903.

    Article  CAS  PubMed  Google Scholar 

  43. Grau E, Moroz LA. Fibrinolytic activity of normal human blood monocytes. Thromb Res. 1989;53:145–62.

    Article  CAS  PubMed  Google Scholar 

  44. Manchanda N, Schwartz BS. Lipopolysaccharide-induced modulation of human monocyte urokinase production and activity. J Immunol. 1990;145:4174–80.

    CAS  PubMed  Google Scholar 

  45. Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266.

    Article  CAS  PubMed  Google Scholar 

  46. Duffy MJ. The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des. 2004;10:39–49.

    Article  CAS  PubMed  Google Scholar 

  47. Lijnen HR, Van Hoef B, Collen D. Activation with plasmin of two-chain urokinase-type plasminogen activator derived from single-chain urokinase-type plasminogen activator by treatment with thrombin. Eur J Biochem. 1987;169:359–64.

    Article  CAS  PubMed  Google Scholar 

  48. Bernik MB. Increased plasminogen activator (urokinase) in tissue culture after fibrin deposition. J Clin Invest. 1973;52:823–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Baeten KM, Richard MC, Kanse SM, Mutch NJ, Degen JL, Booth NA. Activation of single-chain urokinase-type plasminogen activator by platelet-associated plasminogen: a mechanism for stimulation of fibrinolysis by platelets. J Thromb Haemost. 2010;8:1313–22.

    Article  CAS  PubMed  Google Scholar 

  50. Ichinose A, Fujikawa K, Suyama T. The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem. 1986;261:3486–9.

    CAS  PubMed  Google Scholar 

  51. Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem. 1982;257:3276–83.

    CAS  PubMed  Google Scholar 

  52. Darras V, Thienpont M, Stump DC, Collen D. Measurement of urokinase-type plasminogen activator (u-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies. Thromb Haemost. 1986;56:411–4.

    CAS  PubMed  Google Scholar 

  53. Andreotti F, Kluft C. Circadian variation of fibrinolytic activity in blood. Chronobiol Int. 1991;8:336–51.

    Article  CAS  PubMed  Google Scholar 

  54. Levi M, ten Cate JW, Dooijewaard G, Sturk A, Brommer EJ, Agnelli G. DDAVP induces systemic release of urokinase-type plasminogen activator. Thromb Haemost. 1989;62:686–9.

    CAS  PubMed  Google Scholar 

  55. Dooijewaard G, de Boer A, Turion PN, Cohen AF, Breimer DD, Kluft C. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma. Thromb Haemost. 1991;65:82–6.

    CAS  PubMed  Google Scholar 

  56. Bennett B, Booth NA, Croll A, Dawson AA. The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination. Br J Haematol. 1989;71:511–7.

    Article  CAS  PubMed  Google Scholar 

  57. Booth NA, Anderson JA, Bennett B. Plasminogen activators in alcoholic cirrhosis: demonstration of increased tissue type and urokinase type activator. J Clin Pathol. 1984;37:772–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. van der Kaaden MERD, Van Berkel TJC, et al. Plasma clearance of urokinase-type plasminogen activator. Fibrinolysis Proteol. 1998;12:251–8.

    Article  Google Scholar 

  59. Kounnas MZ, Henkin J, Argraves WS, Strickland DK. Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor mediates cellular uptake of pro-urokinase. J Biol Chem. 1993;268:21862–7.

    CAS  PubMed  Google Scholar 

  60. Nykjaer A, Kjoller L, Cohen RL, Lawrence DA, Garni-Wagner BA, Todd 3rd RF, van Zonneveld AJ, Gliemann J, Andreasen PA. Regions involved in binding of urokinase-type-1 inhibitor complex and pro-urokinase to the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that the urokinase receptor protects pro-urokinase against binding to the endocytic receptor. J Biol Chem. 1994;269:25668–76.

    CAS  PubMed  Google Scholar 

  61. Smith SA, Mutch NJ, Baskar D, Rohloff P, Docampo R, Morrissey JH. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006;103:903–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Muller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, Schmidbauer S, Gahl WA, Morrissey JH, Renne T. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139:1143–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kannemeier C, Shibamiya A, Nakazawa F, Trusheim H, Ruppert C, Markart P, Song Y, Tzima E, Kennerknecht E, Niepmann M, von Bruehl ML, Sedding D, Massberg S, Gunther A, Engelmann B, Preissner KT. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci U S A. 2007;104:6388–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Maas C, Govers-Riemslag JW, Bouma B, Schiks B, Hazenberg BP, Lokhorst HM, Hammarstrom P, ten Cate H, de Groot PG, Bouma BN, Gebbink MF. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest. 2008;118:3208–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. van der Meijden PE, Munnix IC, Auger JM, Govers-Riemslag JW, Cosemans JM, Kuijpers MJ, Spronk HM, Watson SP, Renne T, Heemskerk JW. Dual role of collagen in factor XII-dependent thrombus formation. Blood. 2009;114:881–90.

    Article  PubMed  CAS  Google Scholar 

  66. Shore JD, Day DE, Bock PE, Olson ST. Acceleration of surface-dependent autocatalytic activation of blood coagulation factor XII by divalent metal ions. Biochemistry. 1987;26:2250–8.

    Article  CAS  PubMed  Google Scholar 

  67. Schousboe I. The inositol-phospholipid-accelerated activation of prekallikrein by activated factor XII at physiological ionic strength requires zinc ions and high-Mr kininogen. Eur J Biochem. 1990;193:495–9.

    Article  CAS  PubMed  Google Scholar 

  68. Bernardo MM, Day DE, Halvorson HR, Olson ST, Shore JD. Surface-independent acceleration of factor XII activation by zinc ions. II. Direct binding and fluorescence studies. J Biol Chem. 1993;268:12477–83.

    CAS  PubMed  Google Scholar 

  69. Bernardo MM, Day DE, Olson ST, Shore JD. Surface-independent acceleration of factor XII activation by zinc ions. I. Kinetic characterization of the metal ion rate enhancement. J Biol Chem. 1993;268:12468–76.

    CAS  PubMed  Google Scholar 

  70. Shimada T, Kato H, Iwanaga S. Accelerating effect of zinc ions on the surface-mediated activation of factor XII and prekallikrein. J Biochem (Tokyo). 1987;102:913–21.

    CAS  Google Scholar 

  71. Greengard JS, Griffin JH. Receptors for high molecular weight kininogen on stimulated washed human platelets. Biochemistry. 1984;23:6863–9.

    Article  CAS  PubMed  Google Scholar 

  72. Zini JM, Schmaier AH, Cines DB. Bradykinin regulates the expression of kininogen binding sites on endothelial cells. Blood. 1993;81:2936–46.

    CAS  PubMed  Google Scholar 

  73. Herwald H, Morgelin M, Svensson HG, Sjobring U. Zinc-dependent conformational changes in domain D5 of high molecular mass kininogen modulate contact activation. Eur J Biochem. 2001;268:396–404.

    Article  CAS  PubMed  Google Scholar 

  74. McMullen BA, Fujikawa K. Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor). J Biol Chem. 1985;260:5328–41.

    CAS  PubMed  Google Scholar 

  75. Tans G, Rosing J. Structural and functional characterization of factor XII. Semin Thromb Hemost. 1987;13:1–14.

    Article  CAS  PubMed  Google Scholar 

  76. Goldsmith Jr GH, Saito H, Ratnoff OS. The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments. J Clin Invest. 1978;62:54–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Miles LA, Greengard JS, Griffin JH. A comparison of the abilities of plasma kallikrein, beta-Factor XIIa, Factor XIa and urokinase to activate plasminogen. Thromb Res. 1983;29:407–17.

    Article  CAS  PubMed  Google Scholar 

  78. Schousboe I. Factor XIIa activation of plasminogen is enhanced by contact activating surfaces and Zn2+. Blood Coagul Fibrinolysis. 1997;8:97–104.

    Article  CAS  PubMed  Google Scholar 

  79. Levi M, Hack CE, de Boer JP, Brandjes DP, Buller HR, ten Cate JW. Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo. J Clin Invest. 1991;88:1155–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Binnema DJ, Dooijewaard G, Turion PN. An analysis of the activators of single-chain urokinase-type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction of normal plasma and of plasmas deficient in factor XII and prekallikrein. Thromb Haemost. 1991;65:144–8.

    CAS  PubMed  Google Scholar 

  81. Motta G, Rojkjaer R, Hasan AA, Cines DB, Schmaier AH. High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation. Blood. 1998;91:516–28.

    CAS  PubMed  Google Scholar 

  82. Smith D, Gilbert M, Owen WG. Tissue plasminogen activator release in vivo in response to vasoactive agents. Blood. 1985;66:835–9.

    CAS  PubMed  Google Scholar 

  83. Brown NJ, Nadeau JH, Vaughan DE. Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin. Thromb Haemost. 1997;77:522–5.

    CAS  PubMed  Google Scholar 

  84. Huntington JA. Serpin structure, function and dysfunction. J Thromb Haemost. 2011;9 Suppl 1:26–34.

    Article  CAS  PubMed  Google Scholar 

  85. Madison EL, Goldsmith EJ, Gerard RD, Gething MJ, Sambrook JF. Serpin-resistant mutants of human tissue-type plasminogen activator. Nature. 1989;339:721–4.

    Article  CAS  PubMed  Google Scholar 

  86. Manchanda N, Schwartz BS. Interaction of single-chain urokinase and plasminogen activator inhibitor type 1. J Biol Chem. 1995;270:20032–5.

    Article  CAS  PubMed  Google Scholar 

  87. Goldsmith EJ, Sheng-Cheng C, Danley DE, Gerard RD, Geoghegan KF, Mottonen J, Strand A. Preliminary X-ray analysis of crystals of plasminogen activator inhibitor-1. Proteins. 1991;9:225–7.

    Article  CAS  PubMed  Google Scholar 

  88. Hekman CM, Loskutoff DJ. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem. 1985;260:11581–7.

    CAS  PubMed  Google Scholar 

  89. Konkle BA, Schick PK, He X, Liu RJ, Mazur EM. Plasminogen activator inhibitor-1 mRNA is expressed in platelets and megakaryocytes and the megakaryoblastic cell line CHRF-288. Arterioscler Thromb. 1993;13:669–74.

    Article  CAS  PubMed  Google Scholar 

  90. van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. J Biol Chem. 1984;259:14914–21.

    PubMed  Google Scholar 

  91. Cwikel BJ, Barouski-Miller PA, Coleman PL, Gelehrter TD. Dexamethasone induction of an inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1984;259:6847–51.

    CAS  PubMed  Google Scholar 

  92. Morange PE, Alessi MC, Verdier M, Casanova D, Magalon G, Juhan-Vague I. PAI-1 produced ex vivo by human adipose tissue is relevant to PAI-1 blood level. Arterioscler Thromb Vasc Biol. 1999;19:1361–5.

    Article  CAS  PubMed  Google Scholar 

  93. Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol. 1998;18:1–6.

    Article  CAS  PubMed  Google Scholar 

  94. Crandall DL, Quinet EM, Morgan GA, Busler DE, McHendry-Rinde B, Kral JG. Synthesis and secretion of plasminogen activator inhibitor-1 by human preadipocytes. J Clin Endocrinol Metab. 1999;84:3222–7.

    Article  CAS  PubMed  Google Scholar 

  95. Declerck PJ, De Mol M, Alessi MC, Baudner S, Paques EP, Preissner KT, Muller-Berghaus G, Collen D. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J Biol Chem. 1988;263:15454–61.

    CAS  PubMed  Google Scholar 

  96. Kruithof EK, Gudinchet A, Bachmann F. Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb Haemost. 1988;59:7–12.

    CAS  PubMed  Google Scholar 

  97. Booth NA, Simpson AJ, Croll A, Bennett B, MacGregor IR. Plasminogen activator inhibitor (PAI-1) in plasma and platelets. Br J Haematol. 1988;70:327–33.

    Article  CAS  PubMed  Google Scholar 

  98. Declerck PJ, Alessi MC, Verstreken M, Kruithof EK, Juhan-Vague I, Collen D. Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood. 1988;71:220–5.

    CAS  PubMed  Google Scholar 

  99. Andreotti F, Davies GJ, Hackett DR, Khan MI, De Bart AC, Aber VR, Maseri A, Kluft C. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol. 1988;62:635–7.

    Article  CAS  PubMed  Google Scholar 

  100. Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation. 1989;79:101–6.

    Article  CAS  PubMed  Google Scholar 

  101. Kluft C, Jie AF, Rijken DC, Verheijen JH. Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost. 1988;59:329–32.

    CAS  PubMed  Google Scholar 

  102. Booth NA. The natural inhibitors of fibrinolysis. In: Bloom AL, Forbes CD, Thomas DP, et al., editors. Haemostasis and thrombosis. 3rd ed. Edinburgh: Churchill Livingstone; 1994. p. 699–717.

    Google Scholar 

  103. Johnson SA, Schneider CL. The existence of antifibrinolysin activity in platelets. Science. 1953;117:229–30.

    Article  CAS  PubMed  Google Scholar 

  104. Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EK. Plasminogen activator inhibitor 1: a new prognostic marker in septic shock. Thromb Haemost. 1989;61:459–62.

    CAS  PubMed  Google Scholar 

  105. Vaughan DE. Plasminogen activator inhibitor-1: a common denominator in cardiovascular disease. J Investig Med. 1998;46:370–6.

    CAS  PubMed  Google Scholar 

  106. Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation. 1996;94:2057–63.

    Article  CAS  PubMed  Google Scholar 

  107. Carroll VA, Binder BR. The role of the plasminogen activation system in cancer. Semin Thromb Hemost. 1999;25:183–97.

    Article  CAS  PubMed  Google Scholar 

  108. Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrieres J, Arveiler D, Juhan-Vague I. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost. 1998;80:749–56.

    CAS  PubMed  Google Scholar 

  109. Dawson S, Hamsten A, Wiman B, Henney A, Humphries S. Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb. 1991;11:183–90.

    Article  CAS  PubMed  Google Scholar 

  110. Eriksson P, Kallin B. van 't Hooft FM, Bavenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A. 1995;92:1851–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Lowe GD, Yarnell JW, Sweetnam PM, Rumley A, Thomas HF, Elwood PC. Fibrin D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, and the risk of major ischaemic heart disease in the Caerphilly Study. Thromb Haemost. 1998;79:129–33.

    CAS  PubMed  Google Scholar 

  112. Dieval J, Nguyen G, Gross S, Delobel J, Kruithof EK. A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1. Blood. 1991;77:528–32.

    CAS  PubMed  Google Scholar 

  113. Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D. Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med. 1992;327:1729–33.

    Article  CAS  PubMed  Google Scholar 

  114. Lee MH, Vosburgh E, Anderson K, McDonagh J. Deficiency of plasma plasminogen activator inhibitor 1 results in hyperfibrinolytic bleeding. Blood. 1993;81:2357–62.

    CAS  PubMed  Google Scholar 

  115. Fay WP, Parker AC, Condrey LR, Shapiro AD. Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997;90:204–8.

    CAS  PubMed  Google Scholar 

  116. Wiman B, Collen D. On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem. 1978;84:573–8.

    Article  CAS  PubMed  Google Scholar 

  117. Mast AE, Enghild JJ, Pizzo SV, Salvesen G. Analysis of the plasma elimination kinetics and conformational stabilities of native, proteinase-complexed, and reactive site cleaved serpins: comparison of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-antiplasmin, angiotensinogen, and ovalbumin. Biochemistry. 1991;30:1723–30.

    Article  CAS  PubMed  Google Scholar 

  118. Holmes WE, Nelles L, Lijnen HR, Collen D. Primary structure of human alpha 2-antiplasmin, a serine protease inhibitor (serpin). J Biol Chem. 1987;262:1659–64.

    CAS  PubMed  Google Scholar 

  119. Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA. A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion. Blood. 2004;103:3783–8.

    Article  CAS  PubMed  Google Scholar 

  120. Bangert K, Johnsen AH, Christensen U, Thorsen S. Different N-terminal forms of alpha 2-plasmin inhibitor in human plasma. Biochem J. 1993;291(Pt 2):623–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Kimura S, Aoki N. Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor. J Biol Chem. 1986;261:15591–5.

    CAS  PubMed  Google Scholar 

  122. Booth NA. Regulation of fibrinolytic activity by localization of inhibitors to fibrin(ogen). Fibrinolysis Proteol. 2000;14:206–13.

    Article  CAS  Google Scholar 

  123. Sumi Y, Ichikawa Y, Nakamura Y, Miura O, Aoki N. Expression and characterization of pro alpha 2-plasmin inhibitor. J Biochem. 1989;106:703–7.

    CAS  PubMed  Google Scholar 

  124. Reed 3rd GL, Matsueda GR, Haber E. Synergistic fibrinolysis: combined effects of plasminogen activators and an antibody that inhibits alpha 2-antiplasmin. Proc Natl Acad Sci U S A. 1990;87:1114–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Clemmensen I, Thorsen S, Mullertz S, Petersen LC. Properties of three different molecular forms of the alpha 2 plasmin inhibitor. Eur J Biochem. 1981;120:105–12.

    Article  CAS  PubMed  Google Scholar 

  126. Sasaki T, Morita T, Iwanaga S. Identification of the plasminogen-binding site of human alpha 2-plasmin inhibitor. J Biochem. 1986;99:1699–705.

    CAS  PubMed  Google Scholar 

  127. Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost. 1980;43:77–89.

    CAS  PubMed  Google Scholar 

  128. Frank PS, Douglas JT, Locher M, Llinas M, Schaller J. Structural/functional characterization of the alpha 2-plasmin inhibitor C-terminal peptide. Biochemistry. 2003;42:1078–85.

    Article  CAS  PubMed  Google Scholar 

  129. Wang H, Yu A, Wiman B, Pap S. Identification of amino acids in antiplasmin involved in its noncovalent 'lysine-binding-site'-dependent interaction with plasmin. Eur J Biochem. 2003;270:2023–9.

    Article  CAS  PubMed  Google Scholar 

  130. Foley JH, Kim PY, Mutch NJ, Gils A. Insights into thrombin activatable fibrinolysis inhibitor function and regulation. J Thromb Haemost. 2013;11 Suppl 1:306–15.

    Article  PubMed  Google Scholar 

  131. Nesheim M. Fibrinolysis and the plasma carboxypeptidase. Curr Opin Hematol. 1998;5:309–13.

    Article  CAS  PubMed  Google Scholar 

  132. Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. J Biol Chem. 1996;271:16603–8.

    Article  CAS  PubMed  Google Scholar 

  133. Mao SS, Cooper CM, Wood T, Shafer JA, Gardell SJ. Characterization of plasmin-mediated activation of plasma procarboxypeptidase B. Modulation by glycosaminoglycans. J Biol Chem. 1999;274:35046–52.

    Article  CAS  PubMed  Google Scholar 

  134. Bajzar L, Nesheim M, Morser J, Tracy PB. Both cellular and soluble forms of thrombomodulin inhibit fibrinolysis by potentiating the activation of thrombin-activable fibrinolysis inhibitor. J Biol Chem. 1998;273:2792–8.

    Article  CAS  PubMed  Google Scholar 

  135. Bouma BN, Marx PF, Mosnier LO, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Thromb Res. 2001;101:329–54.

    Article  CAS  PubMed  Google Scholar 

  136. Boffa MB, Wang W, Bajzar L, Nesheim ME. Plasma and recombinant thrombin-activable fibrinolysis inhibitor (TAFI) and activated TAFI compared with respect to glycosylation, thrombin/thrombomodulin-dependent activation, thermal stability, and enzymatic properties. J Biol Chem. 1998;273:2127–35.

    Article  CAS  PubMed  Google Scholar 

  137. Leurs J, Wissing BM, Nerme V, Schatteman K, Bjorquist P, Hendriks D. Different mechanisms contribute to the biphasic pattern of carboxypeptidase U (TAFIa) generation during in vitro clot lysis in human plasma. Thromb Haemost. 2003;89:264–71.

    CAS  PubMed  Google Scholar 

  138. Leurs J, Nerme V, Sim Y, Hendriks D. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism. J Thromb Haemost. 2004;2:416–23.

    Article  CAS  PubMed  Google Scholar 

  139. Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M. Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms. Thromb Haemost. 1998;80:949–55.

    CAS  PubMed  Google Scholar 

  140. Brouwers GJ, Vos HL, Leebeek FW, Bulk S, Schneider M, Boffa M, Koschinsky M, van Tilburg NH, Nesheim ME, Bertina RM, Gomez Garcia EB. A novel, possibly functional, single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor (TAFI) gene is also associated with TAFI levels. Blood. 2001;98:1992–3.

    Article  CAS  PubMed  Google Scholar 

  141. Morange PE, Aillaud MF, Nicaud V, Henry M, Juhan-Vague I. Ala147Thr and C + 1542G polymorphisms in the TAFI gene are not associated with a higher risk of venous thrombosis in FV Leiden carriers. Thromb Haemost. 2001;86:1583–4.

    CAS  PubMed  Google Scholar 

  142. Meltzer ME, Lisman T, de Groot PG, Meijers JC, le Cessie S, Doggen CJ, Rosendaal FR. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood. 2010;116:113–21.

    Article  CAS  PubMed  Google Scholar 

  143. Silveira A, Schatteman K, Goossens F, Moor E, Scharpe S, Stromqvist M, Hendriks D, Hamsten A. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease. Thromb Haemost. 2000;84:364–8.

    CAS  PubMed  Google Scholar 

  144. von dem Borne PA, Meijers JC, Bouma BN. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood. 1995;86:3035–42.

    Google Scholar 

  145. Kravtsov DV, Matafonov A, Tucker EI, Sun MF, Walsh PN, Gruber A, Gailani D. Factor XI contributes to thrombin generation in the absence of factor XII. Blood. 2009;114:452–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Bouma BN, Meijers JC. Fibrinolysis and the contact system: a role for factor XI in the down-regulation of fibrinolysis. Thromb Haemost. 1999;82:243–50.

    CAS  PubMed  Google Scholar 

  147. Broze Jr GJ, Higuchi DA. Coagulation-dependent inhibition of fibrinolysis: role of carboxypeptidase-U and the premature lysis of clots from hemophilic plasma. Blood. 1996;88:3815–23.

    CAS  PubMed  Google Scholar 

  148. Mosnier LO, Lisman T, van den Berg HM, Nieuwenhuis HK, Meijers JC, Bouma BN. The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration. Thromb Haemost. 2001;86:1035–9.

    CAS  PubMed  Google Scholar 

  149. Minnema MC, Friederich PW, Levi M, von dem Borne PA, Mosnier LO, Meijers JC, Biemond BJ, Hack CE, Bouma BN, ten Cate H. Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor. J Clin Invest. 1998;101:10–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Astedt B, Lecander I, Brodin T, Lundblad A, Low K. Purification of a specific placental plasminogen activator inhibitor by monoclonal antibody and its complex formation with plasminogen activator. Thromb Haemost. 1985;53:122–5.

    CAS  PubMed  Google Scholar 

  151. Kruithof EK, Vassalli JD, Schleuning WD, Mattaliano RJ, Bachmann F. Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. J Biol Chem. 1986;261:11207–13.

    CAS  PubMed  Google Scholar 

  152. Risse BC, Brown H, Lavker RM, Pearson JM, Baker MS, Ginsburg D, Jensen PJ. Differentiating cells of murine stratified squamous epithelia constitutively express plasminogen activator inhibitor type 2 (PAI-2). Histochem Cell Biol. 1998;110:559–69.

    Article  CAS  PubMed  Google Scholar 

  153. Dougherty KM, Pearson JM, Yang AY, Westrick RJ, Baker MS, Ginsburg D. The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival. Proc Natl Acad Sci U S A. 1999;96:686–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Schwartz BS, Bradshaw JD. Differential regulation of tissue factor and plasminogen activator inhibitor by human mononuclear cells. Blood. 1989;74:1644–50.

    CAS  PubMed  Google Scholar 

  155. Ritchie H, Robbie LA, Kinghorn S, Exley R, Booth NA. Monocyte plasminogen activator inhibitor 2 (PAI-2) inhibits u-PA-mediated fibrin clot lysis and is cross-linked to fibrin. Thromb Haemost. 1999;81:96–103.

    CAS  PubMed  Google Scholar 

  156. Kruithof EK, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987;69:460–6.

    CAS  PubMed  Google Scholar 

  157. Bonnar J, Daly L, Sheppard BL. Changes in the fibrinolytic system during pregnancy. Semin Thromb Hemost. 1990;16:221–9.

    Article  CAS  PubMed  Google Scholar 

  158. Reith A, Booth NA, Moore NR, Cruickshank DJ, Bennett B. Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole. Br J Obstet Gynaecol. 1993;100:370–4.

    Article  CAS  PubMed  Google Scholar 

  159. Grancha S, Estelles A, Gilabert J, Chirivella M, Espana F, Aznar J. Decreased expression of PAI-2 mRNA and protein in pregnancies complicated with intrauterine fetal growth retardation. Thromb Haemost. 1996;76:761–7.

    CAS  PubMed  Google Scholar 

  160. Scherrer A, Kruithof EK, Grob JP. Plasminogen activator inhibitor-2 in patients with monocytic leukemia. Leukemia. 1991;5:479–86.

    CAS  PubMed  Google Scholar 

  161. Robbie LA, Dummer S, Booth NA, Adey GD, Bennett B. Plasminogen activator inhibitor 2 and urokinase-type plasminogen activator in plasma and leucocytes in patients with severe sepsis. Br J Haematol. 2000;109:342–8.

    Article  CAS  PubMed  Google Scholar 

  162. Mueller BM, Yu YB, Laug WE. Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. Proc Natl Acad Sci U S A. 1995;92:205–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Varro A, Noble PJ, Pritchard DM, Kennedy S, Hart CA, Dimaline R, Dockray GJ. Helicobacter pylori induces plasminogen activator inhibitor 2 in gastric epithelial cells through nuclear factor-kappaB and RhoA: implications for invasion and apoptosis. Cancer Res. 2004;64:1695–702.

    Article  CAS  PubMed  Google Scholar 

  164. Huisman LG, van Griensven JM, Kluft C. On the role of C1-inhibitor as inhibitor of tissue-type plasminogen activator in human plasma. Thromb Haemost. 1995;73:466–71.

    CAS  PubMed  Google Scholar 

  165. Miles LA, Hawley SB, Baik N, Andronicos NM, Castellino FJ, Parmer RJ. Plasminogen receptors: the sine qua non of cell surface plasminogen activation. Front Biosci. 2005;10:1754–62.

    CAS  PubMed  Google Scholar 

  166. Miles LA, Plow EF. Binding and activation of plasminogen on the platelet surface. J Biol Chem. 1985;260:4303–11.

    CAS  PubMed  Google Scholar 

  167. Miles LA, Parmer RJ. Plasminogen receptors: the first quarter century. Semin Thromb Hemost. 2013;39:329–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Cheng XF, Brohlin M, Pohl G, Back O, Wallen P. Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA. Thromb Res. 1995;77:149–64.

    Article  CAS  PubMed  Google Scholar 

  169. Razzaq TM, Bass R, Vines DJ, Werner F, Whawell SA, Ellis V. Functional regulation of tissue plasminogen activator on the surface of vascular smooth muscle cells by the type-II transmembrane protein p63 (CKAP4). J Biol Chem. 2003;278:42679–85.

    Article  CAS  PubMed  Google Scholar 

  170. Behrendt N, Ronne E, Dano K. The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface. Biol Chem Hoppe Seyler. 1995;376:269–79.

    CAS  PubMed  Google Scholar 

  171. Webb DJ, Nguyen DH, Gonias SL. Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion. J Cell Sci. 2000;113(Pt 1):123–34.

    CAS  PubMed  Google Scholar 

  172. Wei Y, Yang X, Liu Q, Wilkins JA, Chapman HA. A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. J Cell Biol. 1999;144:1285–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Wienke D, MacFadyen JR, Isacke CM. Identification and characterization of the endocytic transmembrane glycoprotein Endo180 as a novel collagen receptor. Mol Biol Cell. 2003;14:3592–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Kjoller L, Engelholm LH, Hoyer-Hansen M, Dano K, Bugge TH, Behrendt N. uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV. Exp Cell Res. 2004;293:106–16.

    Article  CAS  PubMed  Google Scholar 

  175. Ellis V. Functional analysis of the cellular receptor for urokinase in plasminogen activation. Receptor binding has no influence on the zymogenic nature of pro-urokinase. J Biol Chem. 1996;271:14779–84.

    CAS  PubMed  Google Scholar 

  176. Nykjaer A, Conese M, Christensen EI, Olson D, Cremona O, Gliemann J, Blasi F. Recycling of the urokinase receptor upon internalization of the uPA:serpin complexes. EMBO J. 1997;16:2610–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Ellis V, Scully MF, Kakkar VV. Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem. 1989;264:2185–8.

    CAS  PubMed  Google Scholar 

  178. Manchanda N, Schwartz BS. Single chain urokinase. Augmentation of enzymatic activity upon binding to monocytes. J Biol Chem. 1991;266:14580–4.

    CAS  PubMed  Google Scholar 

  179. Lee SW, Ellis V, Dichek DA. Characterization of plasminogen activation by glycosylphosphatidylinositol-anchored urokinase. J Biol Chem. 1994;269:2411–8.

    CAS  PubMed  Google Scholar 

  180. Dejouvencel T, Doeuvre L, Lacroix R, Plawinski L, Dignat-George F, Lijnen HR, Angles-Cano E. Fibrinolytic cross-talk: a new mechanism for plasmin formation. Blood. 2010;115:2048–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Mitchell JL, Lionikiene AS, Fraser SR. Whyte CS. Mutch NJ. Functional factor XIII-A is exposed on the stimulated platelet surface. Blood: Booth NA; 2014.

    Google Scholar 

  182. Brogren H, Karlsson L, Andersson M, Wang L, Erlinge D, Jern S. Platelets synthesize large amounts of active plasminogen activator inhibitor 1. Blood. 2004;104:3943–8.

    Article  CAS  PubMed  Google Scholar 

  183. Weyrich AS, Schwertz H, Kraiss LW, Zimmerman GA. Protein synthesis by platelets: historical and new perspectives. J Thromb Haemost. 2009;7:241–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Plow EF, Collen D. The presence and release of alpha 2-antiplasmin from human platelets. Blood. 1981;58:1069–74.

    CAS  PubMed  Google Scholar 

  185. Schadinger SL, Lin JH, Garand M, Boffa MB. Secretion and antifibrinolytic function of thrombin-activatable fibrinolysis inhibitor from human platelets. J Thromb Haemost. 2010;8:2523–9.

    Article  CAS  PubMed  Google Scholar 

  186. Robbie LA, Bennett B, Croll AM, Brown PA, Booth NA. Proteins of the fibrinolytic system in human thrombi. Thromb Haemost. 1996;75:127–33.

    CAS  PubMed  Google Scholar 

  187. Potter van Loon BJ, Rijken DC, Brommer EJ, van der Maas AP. The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex-vivo lysibility. Thromb Haemost. 1992;67:101–5.

    CAS  PubMed  Google Scholar 

  188. Mutch NJ, Robbie LA, Booth NA. Human thrombi contain an abundance of active thrombin. Thromb Haemost. 2001;86:1028–34.

    CAS  PubMed  Google Scholar 

  189. Mutch NJ, Moir E, Robbie LA, Berry SH, Bennett B, Booth NA. Localization and identification of thrombin and plasminogen activator activities in model human thrombi by in situ zymography. Thromb Haemost. 2002;88:996–1002.

    CAS  PubMed  Google Scholar 

  190. Moir E, Booth NA, Bennett B, Robbie LA. Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u-PA-dependent mechanism. Br J Haematol. 2001;113:72–80.

    Article  CAS  PubMed  Google Scholar 

  191. Moir E, Robbie LA, Bennett B, Booth NA. Polymorphonuclear leucocytes have two opposing roles in fibrinolysis. Thromb Haemost. 2002;87:1006–10.

    CAS  PubMed  Google Scholar 

  192. Pluskota E, Soloviev DA, Bdeir K, Cines DB, Plow EF. Integrin alphaMbeta2 orchestrates and accelerates plasminogen activation and fibrinolysis by neutrophils. J Biol Chem. 2004;279:18063–72.

    Article  CAS  PubMed  Google Scholar 

  193. Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boelhouwer B, Smith A. Failure of thrombus to resolve in urokinase-type plasminogen activator gene-knockout mice: rescue by normal bone marrow-derived cells. Circulation. 2003;107:869–75.

    Article  CAS  PubMed  Google Scholar 

  194. McGuinness CL, Humphries J, Waltham M, Burnand KG, Collins M, Smith A. Recruitment of labelled monocytes by experimental venous thrombi. Thromb Haemost. 2001;85:1018–24.

    CAS  PubMed  Google Scholar 

  195. Humphries J, Gossage JA, Modarai B, Burnand KG, Sisson TH, Murdoch C, Smith A. Monocyte urokinase-type plasminogen activator up-regulation reduces thrombus size in a model of venous thrombosis. J Vasc Surg. 2009;50:1127–34.

    Article  PubMed  PubMed Central  Google Scholar 

  196. Thorsen S. The mechanism of plasminogen activation and the variability of the fibrin effector during tissue-type plasminogen activator-mediated fibrinolysis. Ann N Y Acad Sci. 1992;667:52–63.

    Article  CAS  PubMed  Google Scholar 

  197. Rijken DC, Sakharov DV. Basic principles in thrombolysis: regulatory role of plasminogen. Thromb Res. 2001;103 Suppl 1:S41–9.

    Article  CAS  PubMed  Google Scholar 

  198. Longstaff C, Thelwell C, Williams SC, Silva MM, Szabo L, Kolev K. The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: kinetic and microscopic studies. Blood. 2010.

    Google Scholar 

  199. Mutch NJ, Moore NR, Wang E, Booth NA. Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI. J Thromb Haemost. 2003;1:2000–7.

    Article  CAS  PubMed  Google Scholar 

  200. Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, Greenlee R. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vitro and in two animal species. J Clin Invest. 1984;73:1731–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Schwartz BS, Espana F. Two distinct urokinase-serpin interactions regulate the initiation of cell surface-associated plasminogen activation. J Biol Chem. 1999;274:15278–83.

    Article  CAS  PubMed  Google Scholar 

  202. Mutch NJ, Koikkalainen JS, Fraser SR, Duthie KM, Griffin M, Mitchell J, Watson HG, Booth NA. Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis. J Thromb Haemost. 2010;8:2017–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Rijken DC, Hoegee-de Nobel E, Jie AF, Atsma DE, Schalij MJ, Nieuwenhuizen W. Development of a new test for the global fibrinolytic capacity in whole blood. J Thromb Haemost. 2008;6:151–7.

    Article  CAS  PubMed  Google Scholar 

  204. Rijken DC, Kock EL, Guimaraes AH, Talens S, Darwish Murad S, Janssen HL, Leebeek FW. Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests. J Thromb Haemost. 2012;10:2116–22.

    Article  CAS  PubMed  Google Scholar 

  205. Ratnoff OD. Some relationships among hemostasis, fibrinolytic phenomena, immunity, and the inflammatory response. Adv Immunol. 1969;10:145–227.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicola J. Mutch Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Mutch, N.J., Booth, N.A. (2016). Plasmin-Antiplasmin System. In: Gonzalez, E., Moore, H., Moore, E. (eds) Trauma Induced Coagulopathy. Springer, Cham. https://doi.org/10.1007/978-3-319-28308-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-28308-1_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-28306-7

  • Online ISBN: 978-3-319-28308-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics