Download PDF
Thromb Haemost 1988; 60(01): 054-058
DOI: 10.1055/s-0038-1647634
Original Article
Schattauer GmbH Stuttgart

Effect of Lupus Anticoagulant on Antithrombogenic Properties of Endothelial Cells - Inhibition of Thrombomodulin-Dependent Protein C Activation

Roger Cariou
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
2   The CHU de Nantes, Hôtel Dieu, Service Hématologie Clinique, Nantes, France
,
Gérard Tobelem
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
,
Sylvia Bellucci
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
,
Jeannette Soria
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
,
Claudine Soria
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
,
Jacques Maclouf
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
,
Jacques Caen
1   The INSERM U 150, CNRS UA 334 - Hôpital Lariboisière, Paris, France
› Author Affiliations
Further Information

Publication History

Received 23 November 1987

Accepted after revision 31 March 1988

Publication Date:
30 June 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient’s IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient’s IgG.

The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient’s IgG or Fab’ fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient’s IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.

Key words

Lupus anticoagulant - Endothelial cells - Protein C - Thrombomodulin - Prostacyclin
 

  • References

  • 1 Frich PG. Acquired circulating anticoagulants in systemic “collagen disease” autoimmune thromboplastin deficiency. Blood 1955; 10: 691-693
    CrossrefPubMedSearch in Google Scholar
  • 2 Harris EN, Gharave AE, Boey ML, Patel BM, Mac Kunth Young CG, Loizou S, Hughes GRV. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; II: 1211-1214
    PubMedSearch in Google Scholar
  • 3 Shoenfeld Y, Rauch J, Massicatte H, Data SK, Schwartz J, Stollar D, Schwartz AS. Polyspecificity of monoclonal lupus antibodies produced by human hybridromas. N Engl J Med 1983; 308: 414-420
    CrossrefPubMedSearch in Google Scholar
  • 4 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980; 92: 156-159
    CrossrefPubMedSearch in Google Scholar
  • 5 Lechner K. Acquired inhibitors in non hemophilic patients. Haemostasis 1984; 3: 65-93
    PubMedSearch in Google Scholar
  • 6 Boey ML, Colaco CB, Charair AE, Elkon KB, Loizou S, Hugues GRV. Thrombosis in SLE: striking association with the presence of circulating lupus anticoagulant. Br Med J 1983; 287: 1021-1023
    CrossrefPubMedSearch in Google Scholar
  • 7 Carreras LO, Defreyn G, Machin SJ, Vermylen J, Deman R, Spitz B, Van AsscheA. Arterial thrombosis, intrauterine death and “lupus” anticoagulant: detection of immunoglobulin interfering with pros-tacyclin formation. Lancet 1981; I: 244-246
    PubMedSearch in Google Scholar
  • 8 Cines DB, Lyss AP, Reeber M, Bian M, Deharatus J. Presence of complement fixing antiendothelial cell antibodies in SLE. J Clin Invest 1984; 73: 611-625
    CrossrefPubMedSearch in Google Scholar
  • 9 Ryken DC, Van Hinsberg VW M. Quantitation of tissue plasminogen activator in human endothelial cell cultures by use of an enzyme immunoassay. Thromb Res 1984; 33: 145-153
    CrossrefPubMedSearch in Google Scholar
  • 10 Owen WG, Esmon CT. Functionnal properties of an endothelial cell cofactor for thrombin catalized activation of protein C. J Biol Chem 1981; 256: 5232-5535
    PubMedSearch in Google Scholar
  • 11 Esmon NL, De Bault LE, Esmon CT. Proteolytic formation and properties of carboxyglutamic acid domain less protein C. J Biol Chem 1983; 258: 5548-5553
    PubMedSearch in Google Scholar
  • 12 Esmon NL, Owen WG, Esmon CT. Isolation of a membrane bound cofactor for thrombin catalyzed activation of protein C. J Biol Chem 1982; 257: 859-864
    PubMedSearch in Google Scholar
  • 13 Caen J, Larrieu MJ, Samama M. L’hémostase: méthodes d’exploration et diagnostic pratique. L’Expansion Scientifique; Paris: 1975. 1 Vol
    Search in Google Scholar
  • 14 Hardisty RM, Ingram GI C. Bleeding Disorders; Blackwell, Oxford: 1965: 315 pp
  • 15 Goudswaard J, Van Der Donk JA, Noordzij A, Van Dam RH, Vaerman J. Protein A reactivity of various mammalian immunoglobulins. Scand J Immunol 1978; 8: 21-28
    CrossrefPubMedSearch in Google Scholar
  • 16 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria J Clin Invest 1983; 52: 2745-2756
    PubMedSearch in Google Scholar
  • 17 Pradelles P, Gassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay. Anal Chem 1985; 57: 1170-1173
    CrossrefPubMedSearch in Google Scholar
  • 18 Engwall E, Carlsson HE. Enzyme linked immunoadsorbent assay Elisa. In: First International Symposium on Immunoenzymatic Technique INSERM Symposium No. 2. Feldmann M. (ed) North-Holland Publishing Company; Amsterdam: 1976. pp 135-147
    Search in Google Scholar
  • 19 Wiman B, Melbring G, Ranby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1982; 127: 279-280
    PubMedSearch in Google Scholar
  • 20 Verheijen JH, Chang GT G, 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
    PubMedSearch in Google Scholar
  • 21 Johnson AJ, Esmon NL, Lane TM, Esmon CT. Structural charges required for activation of protein C are induced by Ca++ binding to a high affinity site that does not contain carboxyglutamic acid. J Biol Chem 1983; 258: 5554-5560
    PubMedSearch in Google Scholar
  • 22 Salem HH, Maruyana I, Ishii H, Majerus PW. Isolation and characterization of thrombomodulin from human placenta. J Biol Chem 1984; 259: 12246-12251
    PubMedSearch in Google Scholar
  • 23 Shapiro SS, Thiagarajan P. Lupus anticoagulants. Prog Thromb Haemostas 1982; 6: 263-283
    PubMedSearch in Google Scholar
  • 24 Kelsey PR, Stevenson KJ, Poller L. The diagnosis of lupus anticoagulants by the activated partial thromboplastin time. The central role of phosphotidylserine. Thromb Haemostas 1984; 52: 172-175
    PubMedSearch in Google Scholar
  • 25 Thiagarjan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin M coagulation inhibitor with phospholipid specificity. J Clin Invest 1980; 66: 397-405
    CrossrefPubMedSearch in Google Scholar
  • 26 Goldsmith JC, Cormick JJ. Immunologic injury to vascular endothelial cells. Effect on release of prostacyclin Blood 1984; 63: 984-989
    PubMedSearch in Google Scholar
  • 27 Fitzgerald GA, Smith B, Perdersen AK, Brash AR. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 1984; 310: 1065-1068
    CrossrefPubMedSearch in Google Scholar
  • 28 Wautier JL, Pintigny D, Maclouf J, Wautier MP, Corvazier E, Caen J. Realease of prostacyclin after erythrocyte adhesion to cultured vascular endothelium. J Lab Clin Med 1986; 107: 210-215
    PubMedSearch in Google Scholar
  • 29 Angles Cano E, Sultan Y, Clauvel JP. Predisposing factors to thrombosis in SLE possible relation to endothelial cell damage. J Lab Clin Med 1979; 94: 312-323
    PubMedSearch in Google Scholar
  • 30 Glas Greenwalt P, Shashi Kant K, Allen C, Pollek VE. Fibrinolysis in health and disease: severe abnormalities in SLE. J Lab Clin Med 1984; 104: 962-976
    PubMedSearch in Google Scholar
  • 31 Malar RA, Kleiss AJ, Griffin JH. Mechanism of action of human activated protein C, a thrombin dependent anticoagulant enzyme. Blood 1982; 59: 1067-1072
    PubMedSearch in Google Scholar
  • 32 Van Hinsbergh VW N, Bertessa RM, Van Wijn Gaarden A, Van Tilburg NH, Fineis JJ, Hawerkate F. Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell conditioned medium. Blood 1985; 65: 444-451
    PubMedSearch in Google Scholar
  • 33 Salem HH, Esmon NL, Esmon CT, Mayers PW. Effects of thrombomodulin and coagulation factor Va light chain on protein C activation in vitro. J Clin Invest 1984; 73: 968-972
    CrossrefPubMedSearch in Google Scholar
  • 34 Nixon RR, Comp PC, Esmon CT. Role of Gla-domain in activated protein C. Fed Proc 1983; 42: 1993 (abstract)
    PubMedSearch in Google Scholar
  • 35 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1980; 68: 1370-1373
    PubMedSearch in Google Scholar
  • 36 Freyssinet JM, Brami B, Gauchy J, Cazenave JP. Coextraction of thrombomodulin and tissue factor from human placenta. Effects of concanavalin A and phospholipid environment on activity. Thromb Haemostas 1986; 55: 112-118
    PubMedSearch in Google Scholar
  • 37 Freyssinet JM, Wiesel ML, Gauchy J, Boneu B, Cazenave JP. An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity. A mechanism for thrombosis Thromb Haemostas 1986; 55: 309-313
    PubMedSearch in Google Scholar