Thromb Haemost 1994; 72(04): 578-581
DOI: 10.1055/s-0038-1648918
Original Article
Schattauer GmbH Stuttgart

The Interaction of β2 Glycoprotein-I and Heparin and Its Effect on β2 Glycoprotein-I Antiphospholipid Antibody Cofactor Function in Plasma

T McNally
1   The Department of Haematology, Department of Medicine, University College London Medical School, London, UK
,
S E Cotterell
1   The Department of Haematology, Department of Medicine, University College London Medical School, London, UK
,
I J Mackie
1   The Department of Haematology, Department of Medicine, University College London Medical School, London, UK
,
D A Isenberg
2   Bloomsbury Rheumatology Unit, Department of Medicine, University College London Medical School, London, UK
,
S J Machin
1   The Department of Haematology, Department of Medicine, University College London Medical School, London, UK
› Author Affiliations
Further Information

Publication History

Received 06 April 1994

Accepted after revision 06 June 1994

Publication Date:
06 July 2018 (online)

Summary

β2 glycoprotein-I (β2GPI), a cofactor for antiphospholipid antibody (aPA) binding, binds to many anionic macromolecules including heparin. The nature of this interaction with heparin is not well understood and its effect on the purported biological functions of β2GPI is unknown.

We have examined the interactions of dermatan sulphate (DS) and different pharmaceutical preparations of heparin with β2GPI by crossed immunoelectrophoresis (CIE) and investigated the effect of these agents on plasma levels of p2GPI antigen (β2GPI: Ag) by a standardised enzyme linked immunosorbent assay (ELISA). P2GPI aPA cofactor activity (β2GPI:Cof) was also measured using a modified solid phase an-ti-phosphatidylserine (aPS) ELISA. CIE results confirmed a heparin-β2GPI interaction with unfractionated (UF) heparin. β2GPI:Ag levels were unaffected by any of the preparations investigated. There were no significant differences in β2GPI:Cof activities of the samples containing LMW heparins or DS but levels of β2GPI:Cof were increased in samples containing UF sodium and calcium heparin preparations (0.5 IU/ml Monoparin, p <0.05, and 10 IU/ml Liquemin and Calcipa-rine, p <0.05).

 
  • References

  • 1 Kroll J, Larsen JK, Loft H, Ezban M, Wallewick K, Faber M. DNA binding proteins in Yoshida asites tumor fluid. Biochim Biophys Acta 1976; 434: 490-501
  • 2 Polz E, Kostner GM. The binding of β2 glycoprotein-I to human serum lipoproteins: distribution among density fractions. FEBS Letters 1979; 102: 183-186
  • 3 Schousboe I. Binding of β2 glycoprotein-I to platelets: effect on adenylate cyclase activity. Thromb Res 1980; 19: 225-237
  • 4 Schousboe I. Characterization of the interaction between β2 glycoprotein-I and mitochondria, platelets, liposomes and bile acids. Int J Biochem 1983; 15: 1393-1401
  • 5 Polz E, Wurm H, Kostner GM. Investigations on β2 glycoprotein-I in the rat: isolation from serum and demonstration in lipoprotein density fractions. Int J Biochem 1980; 11: 265-270
  • 6 Schousboe I. β2 glycoprotein-I: A plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway. Blood 1985; 66: 1086-1091
  • 7 Nimpf J, Bevers EM, Bomans PHH, Till U, Wurm H, Kostner GM, Zwaal RFA. Prothrombinase activity of human platelets is inhibited by β2 glyco-protein-I. Biochim Biophys Acta 1986; 884: 142-149
  • 8 Nimpf J, Wurm H, Kostner GM. Interaction of β2 glycoprotein-I with human blood platelets: Influence upon ADP induced aggregation. Thromb Haemost 1985; 54: 397-401
  • 9 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets HM, van Breda-Vriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) are directed not to a cardiolipin but to a plasma protein co-factor. Lancet 1990; 335: 1544-1547
  • 10 McNeil HP, Simpson RJ, Chesterman CN, Krillis SA. Antiphospholipid antibodies are directed a complex antigen that includes a lipid-binding inhibitor of coagulation: β2 glycoprotein-I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120-4124
  • 11 Bowie WEJ, Thompson JH, Pascuzzi CA, Owen GA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Clin Lab Med 1963; 62: 416-430
  • 12 Nilsson IM, Asted B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant, „antithromboplastin‟. Acta Med scand 1975; 197: 153-175
  • 13 Greaves M, Preston FE. Clinical and laboratory aspects of thrombophilia. In: Recent Advances in Blood Coagulation 5 1991. Churchill Livingstone; 119-140
  • 14 Wagenknecht DR, McIntyre J. Interaction of heparin with β2 glycoprotein-I and antiphospholipid antibodies in vitro. Throm Res 1992; 68: 495-500
  • 15 McNally T, Mackie IJ, Isenberg DA, Machin SJ. Immunoelectrophoresis and ELISA techniques for assay of plasma β2 glycoprotein-I and the influence of plasma lipids. Thromb Res 1993; 72: 275-286
  • 16 Viard JP, Amoura Z, Bach JF. Association of anti-pβ2 glycoprotein-I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. The American Journal of Medicine 1992; 93: 181-186
  • 17 Laurell CB. Antigen-antibody crossed electrophoresis. Analytical Biochemistry 1965; 10: 358-361
  • 18 Hirsh J. Mechanism of action and monitoring of anticoagulants. Seminars in Thrombosis and Haemostasis 1986; 12: 1-11
  • 19 Ireland H, Rylance PB, Kesteven P. Heparin as an anticoagulant during ex-tracorporeal circulation. In: Heparin: Chemical and Biological Properties, Clinical Applications Lane DA, Lindahl U. (eds) Edward Arnold; 1989: 549-574
  • 20 Hunt JE, Simpson RJ, Krilis SA. Identification of a region of β2 glyco-protein-I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Natl Acad Sci USA 1993; 90: 2141-2145
  • 21 Wagenknecht DR, McIntyre JA. Changes in β2 glycoprotein-I antigenicity induced by phospholipid binding. Thromb Haemost 1993; 69: 361-365