Download PDF
Thromb Haemost 1992; 68(06): 657-661
DOI: 10.1055/s-0038-1646339
Original Article
Schattauer GmbH Stuttgart

Vitronectin Modulates Glycosaminoglycan Dependent Reactions of Protein C Inhibitor

Dietmar Seiffert
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Margarethe Geiger
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Sonja Ecke
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
,
Bernd R Binder
The Laboratory for Clinical Experimental Physiology, Department of Medical Physiology, University of Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 19 May 1992

Accepted after revision 22 July 1992

Publication Date:
04 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Protein C inhibitor (PCI), a glycosaminoglycan (GAG) dependent serine protease inhibitor, inhibits its target proteases by forming SDS-stable 1:1 complexes. GAGs alter target enzyme specificity of PCI in such a way that e.g. urokinase (uPA) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein (TK) complexes are formed.

The effect of the GAG-binding adhesive glycoprotein vitronectin (Vn) on the GAG-stimulated inhibition of uPA by PCI was studied using an amidolytic assay. In the presence of heparin, Vn protected uPA from inhibition by PCI in a dose-dependent manner with respect to both, Vn- and heparin-concentration. Vn also was active when heparin was replaced by low-molecular weight heparin or heparan sulfate, respectively. In the absence of GAGs, Vn had no effect on the inhibition of uPA by PCI.

In a similar system, Vn was far less effective in modifying the inhibitory function of heparin on the inhibition of TK by PCI. When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin, only complexes of PCI with uPA were detectable. Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared. These results indicate that Vn modulates both, the activity and specificity of PCI and suggest different structural heparin-requirements for the PCI/uPA versus PCI/TK interaction.

 

  • REFERENCES

  • 1 Stief TW, Radtke K-P, Heimburger N. Inhibition of urokinase by protein C inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3. Biol Chem Hoppe-Seyler 1987; 368: 1427-1433
    PubMedGoogle Scholar
  • 2 Heeb MJ, Espana F, Geiger M, Collen D, Stump DC, Griffin JH. Immunological identity of heparin-dependent plasma and urinary protein C inhibitor and plasminogen activator inhibitor-3. J Biol Chem 1987; 15813-15816
    PubMedGoogle Scholar
  • 3 Suzuki K, Nishioka J, Hashimoto S. Protein C inhibitor: purification from human plasma and characterization. J Biol Chem 1983; 258: 163-168
    PubMedGoogle Scholar
  • 4 Stump DC, Thienpont M, Collen D. Purification and characterization of a novel inhibitor of urokinase from human urine. J Biol Chem 1986; 261: 12759-12766
    PubMedGoogle Scholar
  • 5 Geiger M, Priglinger U, Griffin JH, Binder BR. Urinary protein C inhibitor. J Biol Chem 1991; 266: 11851-11857
    PubMedGoogle Scholar
  • 6 Suzuki K, Nishioka J, Kusumoto H, Hashimoto S. Mechanism of inhibition of activated protein C by protein C inhibitor. J Biochem 1984; 95: 187-195
    CrossrefPubMedGoogle Scholar
  • 7 Meijers JCM, Kanters DHAJ, Vlooswijk RAA, van Erp HE, Hessing M, Bouma BN. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry 1988; 27: 4231-4237
    CrossrefPubMedGoogle Scholar
  • 8 Scicli AG, Carretero OA. Renal kallikrein-kinin system. Kidney Int 1986; 29: 120-130
    CrossrefPubMedGoogle Scholar
  • 9 Ecke S, Geiger M, Resch I, Jerabek I, Stingl L, Maier M, Binder BR. Inhibition of tissue kallikrein by protein C inhibitor. J Biol Chem 1992; 267: 7048-7052
    PubMedGoogle Scholar
  • 10 Hayman EG, Pierschbacher MD, Ohgren Y, Ruoslahti E. Serum spreading factor (vitronectin) is present at the cell surface and in tissues. Proc Natl Acad Sci USA 1983; 80: 4003-4007
    CrossrefPubMedGoogle Scholar
  • 11 Hayman EG, Pierschbacher MD, Suzuki S, Ruoslahti E. Vitronectin - a major cell attachment-promoting protein in fetal bovine serum. Exp Cell Res 1985; 160: 245-258
    CrossrefPubMedGoogle Scholar
  • 12 Tomassini BR, Mosher DF. Vitronectin. In: Progress in Hemostasis and Thrombosis, Vol. 10. Coller BS. (ed) Philadelphia, PA: Saunders: 1990. pp 269-305
    Google Scholar
  • 13 Preisner KT. Structure and biological role of vitronectin. Annu Rev Cell Biol 1991; 7: 275-310
    CrossrefPubMedGoogle Scholar
  • 14 Ill CR, Ruoslahti E. Association of thrombin-antithrombin III complex with vitronectin in serum. J Biol Chem 1985; 260: 15610-15615
    PubMedGoogle Scholar
  • 15 Preissner KT, Mueller-Berghaus G. Neutralization and binding of heparin by S protein/vitronectin in the inhibition of factor Xa by antithrombin III. J Biol Chem 1987; 262: 12247-12253
    PubMedGoogle Scholar
  • 16 Declerk PJ, De Mol M. Alessi M-C, Baudner S, Paques E-P, Preissner KT, Mueller-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: 15454-15461
    PubMedGoogle Scholar
  • 17 Mumuro J, Loskutoff DJ. Purification of a protein from bovine plasma that binds to type 1 plasminogen activator inhibitor and prevents its interaction with extracellular matrix. J Biol Chem 1989; 264: 936-939
    PubMedGoogle Scholar
  • 18 Seiffert D, Loskutoff DJ. Evidence that type 1 plasminogen activator inhibitor binds to the somatomedin B domain of vitronectin. J Biol Chem 1991; 266: 2824-2830
    PubMedGoogle Scholar
  • 19 Ehrlich HJ, Klein Gebbink R, Keijer J, Linders M, Preissner KT, Pannekoek H. Alteration of serpin specificity by a protein cofactor. J Biol Chem 1990; 265: 13029-13035
    PubMedGoogle Scholar
  • 20 Lesuk A, Terminiello L, Travel JH. Crystalline human urokinase: Some properties. Science 1965; 147: 880-882
    CrossrefPubMedGoogle Scholar
  • 21 White WF, Barlow GH, Mozen MM. The isolation and characterization of plasminogen activators (urokinase) from human urine. Biochemistry 1966; 5: 2160-2169
    CrossrefPubMedGoogle Scholar
  • 22 Shafer MC, Foley TP, Barnes DW. Quantification of spreading factor in human biological fluids. J Lab Clin Med 1984; 103: 783-791
    PubMedGoogle Scholar
  • 23 Suzuki K, Deyashiki Y, Nishioka J, Toma K. Protein C inhibitor: Structure and Function. Thromb Haemostas 1989; 61: 337-342
    PubMedGoogle Scholar
  • 24 Yatohgo T, Izumi M, Kashiwagi H, Hauashi M. Novel purification of vitronectin from human plasma by heparin affinity chromotography. Cell Structure and Function 1988; 13: 281-292
    CrossrefPubMedGoogle Scholar
  • 25 Preissner KT, Wassmuth R, Mueller-Berghaus G. Physicochemical characterization of human S-protein and its function in the blood coagulation system. Biochem J 1985; 231: 3349-3355
    PubMedGoogle Scholar
  • 26 Fraker PJ, Speck JC. Protein and cell membrane iodination with a springly soluble chloroamide, 1, 3, 4, 6-tetrachloro-3a, 6a-diphenyl-glycoluril. Biochem Biophys Res Com 1978; 80: 849-857
    CrossrefPubMedGoogle Scholar
  • 27 Ole-Moi Yoi O, Spragg J, Austen KF. Structural studies of human urinary kallikrein. Proc Natl Acad Sci USA 1979; 76: 3121-3125
    CrossrefPubMedGoogle Scholar
  • 28 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
    CrossrefPubMedGoogle Scholar
  • 29 Geiger M. Protein C inhibitor/plasminogen activator inhibitor 3. Fibrinolysis 1988; 2: 183-188
    PubMedGoogle Scholar
  • 30 Preissner KT, Sie P. Modulation of heparin cofactor II function by S protein (vitronectin) and formation of a ternary S protein-thrombin-heparin cofactor II complex. Thromb Haemostas 1989; 60: 399-406
    PubMedGoogle Scholar
  • 31 Handin RI, Cohen HJ. Purification and binding properties of human platelet factor four. J Biol Chem 1976; 251: 4273-4282
    PubMedGoogle Scholar
  • 32 Jordan RE, Favreau LV, Braswell EH, Rosenberg RD. Heparin with two binding sites for antithrombin or platelet factor 4. J Biol Chem 1982; 257: 400-406
    PubMedGoogle Scholar
  • 33 Heimburger N, Haupt H, Kranz T, Baudner S. Humanserumproteine mit hoher Affinität zu Carboxymethylcellulose, II. Physikalischchemische und immunologische Charakterisierung eines histidinreichen 3,8 S-2-alpha-Glykoproteins (CM-Protein I). Hoppe-Seylers Z Physiol Chem 1972; 353: 1133-1140
    PubMedGoogle Scholar
  • 34 Lijnen HR, Hoylaerts M, Collen D. Heparin binding properties of human histidine-rich glycoprotein. Mechanism and role in the neutralization of heparin in plasma. J Biol Chem 1983; 258: 3803-3808
    PubMedGoogle Scholar
  • 35 Lane DA, Flynn AM, Pejler G, Lindahl U, Choay J, Preissner K. Structural requirements for the neutralization of heparin-like saccharides by complement S protein/vitronectin. J Biol Chem 1987; 262: 16343-16348
    PubMedGoogle Scholar
  • 36 Asakura S, Hurley RW, Skorstengaard K, Ohkubo I, Mosher D. Inhibition of cell adhesion by high molecular weight kininogen. J Cell Biol 1992; 116: 465-476
    CrossrefPubMedGoogle Scholar