Synergistic Effect of Low Doses of Tumor Necrosis Factor and Sera from Patients with Systemic Lupus Erythematosus on the Expression of Procoagulant Activity by Cultured Endothelial Cells

Paula Hasselaar; Ronald H W M Derksen; Janine D Oosting; Laya Blokzijl; Philip G de Groot

doi:10.1055/s-0038-1646878

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 62(02): 654-660
DOI: 10.1055/s-0038-1646878

Original Article

Schattauer GmbH Stuttgart

Synergistic Effect of Low Doses of Tumor Necrosis Factor and Sera from Patients with Systemic Lupus Erythematosus on the Expression of Procoagulant Activity by Cultured Endothelial Cells

Paula Hasselaar

¹The Department of Haematology, University Hospital Utrecht, The Netherlands

²The Department of Internal Medicine, Division of Immunopathology, University Hospital Utrecht, The Netherlands

,

Ronald H W M Derksen

²The Department of Internal Medicine, Division of Immunopathology, University Hospital Utrecht, The Netherlands

,

Janine D Oosting

¹The Department of Haematology, University Hospital Utrecht, The Netherlands

,

Laya Blokzijl

¹The Department of Haematology, University Hospital Utrecht, The Netherlands

²The Department of Internal Medicine, Division of Immunopathology, University Hospital Utrecht, The Netherlands

,

Philip G de Groot

¹The Department of Haematology, University Hospital Utrecht, The Netherlands

› Author Affiliations

Abstract

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Summary

The effect of 15 antiphospholipid antibody (APA) positive SLE sera, 13 APA negative SLE sera, 10 APA negative sera from patients with other connective tissue diseases (CTD) and 15 control sera on the expression of endothelial procoagulant activity (PCA) was studied. Endothelial cells (EC) were stimulated with tumor necrosis factor (TNF) and 20% serum for 4 hr and the surface PC A expression was measured. Without TNF, none of the sera stimulated PC A expression. With subop timal TNF stimulation, 14/15 APA positive SLE sera, 7/13 APA negative SLE sera, 2/10 CTD sera and 2/15 control sera enhanced PC A expression. This stimulating effect resided in the IgG fraction and was associated with the presence of APA, but not with a history of thrombosis. Purified APA had no PC A stimulating activity. PC A expression was inhibited by cycloheximide and heat treatment (30 min, 56° C) of serum.

In conclusion, 21/28 (75%) SLE sera increase the TNF-induced endothelial PC A expression. Although this effect predominantly occurs with APA positive serum, a causative role of APA was not demonstrated.

Keywords

Antiphospholipid antibodies - Systemic lupus erythematosus - Procoagulant activity

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References

References
1 Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GR V. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1214
2 Derksen RH W M, Kater L. Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol 1985; 3: 349-357
3 Feinstein DI. Lupus anticoagulant, thrombosis and fetal loss. N Engl J Med 1985; 313: 1348-1350
4 Derksen RH W M, Bouma BN, Kater K. The striking association between lupus anticoagulant and fetal loss in systemic lupus erythematosus. Arthritis Rheum 1986; 29: 695-696
5 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. Haemostasis 1985; 15: 254-262
6 Carreras LO, Vermylen JG. “Lupus” anticoagulant and thrombosis - Possible role of inhibition of prostacyclin formation. Thromb Haemostas 1982; 48: 38-40
7 Hasselaar P, Derksen RH W M, Blokzijl L, de Groot PG. Thrombosis associated with antiphospholipid antibodies cannot be explained by effects on endothelial and platelet prostanoid synthesis. Thromb Haemostas 1988; 59: 80-85
8 Comp PC, De Bault LE, Esmon NE, Esmon CP. Human thrombomodulin is inhibited by IgG from two patients with nonspecific anticoagulants. Blood 1983; 62: 1099
9 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
10 Cariou R, Tobelem G, Bellucci S, Soria J, Soria C, Maclouf J, Caen J. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells - Inhibition of thrombomodulin-dependent protein C activation. Thromb Haemostas 1988; 60: 54-58
11 Francis RB, McGehee WG, Feinstein DI. Endothelial-dependent fibrinolysis in subjects with the lupus anticoagulant and thrombosis. Thromb Haemostas 1988; 59: 412-414
12 Nawroth PP, Handley DA, Esmon CT, Stern DM. Interleukin 1 induces endothelial cell procoagulant activity while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 1986; 83: 3460-3464
13 Colucci M, Balconi G, Lorenzet R, Pietra A, Locati D, Donati MB, Semeraro N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
14 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-745
15 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-4537
16 Galdal KS, Lyberg T, Evensen SA, Nilsen E, Prydz H. Thrombin induces thromboplastin synthesis in cultured vascular endothelial cells. Thromb Haemostas 1985; 54: 373-376
17 Johnsen UL H, Lyberg T, Gaidai KS, Prydz H. Platelets stimulate thromboplastin synthesis in human endothelial cells. Thromb Haemostas 1983; 49: 69-72
18 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-2252
19 Tan EM, Cohen AS, Fries JF, Masi AT, McShane J, Rothfield NF, Green Schaller J, Talal N, Winchester RJ. The 1982 revised criteria for the classification of SLE. Arthritis Rheum 1982; 25: 1271-1277
20 Derksen RH W M, Hasselaar P, Blokzijl L, Gmelig MeylingF H J, de Groot PG. Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis 1988; 47: 364-371
21 Pengo V, Thiagarajan P, Shapiro SS, Heine MJ. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood 1987; 70: 69-76
22 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. J Clin Invest 1973; 52: 2745-2756
23 Willems C, Astaldi GC B, de Groot PG, Janssen MC, Gonsalves MD, Zeijlemaker WP, van Mourik JA, van Aken WG. Media conditioned by cultured human vascular endothelial cells inhibit the growth of vascular smooth muscle cells. Exp Cell Res 1982; 139: 191-197
24 Rothberger H, Zimmerman TS, Spiegelberg HL, Vaughan JH. Leukocyte procoagulant activity. Enhancement of production in vitro by IgG and antigen-antibody complexes. J Clin Invest 1977; 59: 549-557
25 Tannenbaum SH, Finko R, Cines DB. Antibody and immune complexes induce tissue factor production by human endothelial cells. J Immunol 1986; 137: 1532-1537
26 Rustin MH A, Bull HA, Machin SJ, Isenberg DA, Snaith ML, Dowd PM. Effects of the lupus anticoagulant in patients with systemic lupus erythematosus on endothelial cell prostacyclin release and procoagulant activity. J Invest Dermatol 1988; 90: 744-748
27 Rao LV M, Rapaport SI. Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 1987; 69: 645-651
28 Ryan US, Schultz DR, Ryan JW. Fc and C3b receptors on pulmonary endothelial cells: induction by injury. Science 1981; 214: 557-558
29 Daha MR, Miltenburg AM M, Hiemstra PS, Klar-Mohamad N, van Es LA, van Hinsbergh VW M. The complement subcomponent Clq mediates binding of immune complexes and aggregates to endothelial cells. Eur J Immunol 1988; 18: 783-787
30 Leung DY M, Geha RS, Newburger JW, Burns JC, Fiers W, Lapierre LA, Pober JS. Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. J Exp Med 1986; 164: 1958-1972
31 Leung DY M, Collins T, Lapierre LA, Geha RS, Pober JS. Immunoglobulin M antibodies present in the acute phase of Kawasaki syndrome lyse cultured vascular endothelial cells stimulated by gamma interferon. J Clin Invest 1986; 77: 1428-1435
32 Furakawa S, Matsubara T, Jujoh K, Yone K, Sugawara T, Sasai K, Kato H, Yabuta K. Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease. Clin Immunol Immunopathol 1988; 48: 247-251