Abstract
Circulating antiphospholipid antibodies (aPL) are associated with a syndrome of thrombosis, recurrent fetal loss, and thrombocytopenia. We have demonstrated the activation of cultured human umbilical vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation of HUVEC for 4 h with purified IgG (100 micrograms/ml) from patients with high-titer aCL induced a 2.3-fold increase in monocyte adhesion over that seen in HUVEC incubated with IgG's from normal subjects. The effect of aCL was not attributable to LPS contamination, Fc receptors, or immune complexes. Monocyte adhesion was not induced when the aCL were added in serum-free media but was restored by the addition of purified beta 2GP1, previously described as a necessary cofactor for aCL reactivity. Purified rabbit polyclonal IgG raised against beta 2GP1 also induced monocyte adhesion when incubated with HUVEC. Preadsorption of patient serum with cardiolipin reduced monocyte adhesion by 60%. Immunofluorescent microscopy demonstrated that endothelial cells incubated with patient IgG expressed cell adhesion molecules, including E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. These data support the hypothesis that aPL activate vascular endothelial cells, thereby leading to a pro-thrombotic state.
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- Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Branch D. W., Dudley D. J., Mitchell M. D., Creighton K. A., Abbott T. M., Hammond E. H., Daynes R. A. Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss. Am J Obstet Gynecol. 1990 Jul;163(1 Pt 1):210–216. doi: 10.1016/s0002-9378(11)90700-5. [DOI] [PubMed] [Google Scholar]
- 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 Haemost. 1988 Aug 30;60(1):54–58. [PubMed] [Google Scholar]
- Cines D. B., Lyss A. P., Reeber M., Bina M., DeHoratius R. J. Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest. 1984 Mar;73(3):611–625. doi: 10.1172/JCI111251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Papa N., Meroni P. L., Tincani A., Harris E. N., Pierangeli S. S., Barcellini W., Borghi M. O., Balestrieri G., Zanussi C. Relationship between anti-phospholipid and anti-endothelial cell antibodies: further characterization of the reactivity on resting and cytokine-activated endothelial cells. Clin Exp Rheumatol. 1992 Jan-Feb;10(1):37–42. [PubMed] [Google Scholar]
- Gharavi A. E., Harris E. N., Asherson R. A., Hughes G. R. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis. 1987 Jan;46(1):1–6. doi: 10.1136/ard.46.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gharavi A. E., Mellors R. C., Elkon K. B. IgG anti-cardiolipin antibodies in murine lupus. Clin Exp Immunol. 1989 Nov;78(2):233–238. [PMC free article] [PubMed] [Google Scholar]
- Gharavi A. E., Sammaritano L. R., Wen J., Elkon K. B. Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). J Clin Invest. 1992 Sep;90(3):1105–1109. doi: 10.1172/JCI115927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ginsburg K. S., Liang M. H., Newcomer L., Goldhaber S. Z., Schur P. H., Hennekens C. H., Stampfer M. J. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992 Dec 15;117(12):997–1002. doi: 10.7326/0003-4819-117-12-997. [DOI] [PubMed] [Google Scholar]
- Harris E. N., Gharavi A. E., Hughes G. R. Anti-phospholipid antibodies. Clin Rheum Dis. 1985 Dec;11(3):591–609. [PubMed] [Google Scholar]
- Hess D. C., Sheppard J. C., Adams R. J. Increased immunoglobulin binding to cerebral endothelium in patients with antiphospholipid antibodies. Stroke. 1993 Jul;24(7):994–999. doi: 10.1161/01.str.24.7.994. [DOI] [PubMed] [Google Scholar]
- ISHIZAKA K., ISHIZAKA T. Biologic activity of aggregated gamma-globulin. II. A study of various methods for aggregation and species differences. J Immunol. 1960 Aug;85:163–171. [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kornberg A., Blank M., Kaufman S., Shoenfeld Y. Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol. 1994 Aug 1;153(3):1328–1332. [PubMed] [Google Scholar]
- Lindsey N. J., Dawson R. A., Henderson F. I., Greaves M., Hughes P. Stimulation of von Willebrand factor antigen release by immunoglobulin from thrombosis prone patients with systemic lupus erythematosus and the anti-phospholipid syndrome. Br J Rheumatol. 1993 Feb;32(2):123–126. doi: 10.1093/rheumatology/32.2.123. [DOI] [PubMed] [Google Scholar]
- Lo S. K., Cheung A., Zheng Q., Silverstein R. L. Induction of tissue factor on monocytes by adhesion to endothelial cells. J Immunol. 1995 May 1;154(9):4768–4777. [PubMed] [Google Scholar]
- Love P. E., Santoro S. A. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med. 1990 May 1;112(9):682–698. doi: 10.7326/0003-4819-112-9-682. [DOI] [PubMed] [Google Scholar]
- Lozier J., Takahashi N., Putnam F. W. Complete amino acid sequence of human plasma beta 2-glycoprotein I. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3640–3644. doi: 10.1073/pnas.81.12.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCrae K. R., DeMichele A., Samuels P., Roth D., Kuo A., Meng Q. H., Rauch J., Cines D. B. Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies. Br J Haematol. 1991 Dec;79(4):595–605. doi: 10.1111/j.1365-2141.1991.tb08087.x. [DOI] [PubMed] [Google Scholar]
- McNeil H. P., Simpson R. J., Chesterman C. N., Krilis S. A. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A. 1990 Jun;87(11):4120–4124. doi: 10.1073/pnas.87.11.4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nachman R. L., Silverstein R. Hypercoagulable states. Ann Intern Med. 1993 Oct 15;119(8):819–827. doi: 10.7326/0003-4819-119-8-199310150-00008. [DOI] [PubMed] [Google Scholar]
- Polz E., Wurm H., Kostner G. M. Investigations on beta 2-glycoprotein-I in the rat: isolation from serum and demonstration in lipoprotein density fractions. Int J Biochem. 1980;11(3-4):265–270. doi: 10.1016/0020-711x(80)90229-3. [DOI] [PubMed] [Google Scholar]
- Rosenbaum J., Pottinger B. E., Woo P., Black C. M., Loizou S., Byron M. A., Pearson J. D. Measurement and characterisation of circulating anti-endothelial cell IgG in connective tissue diseases. Clin Exp Immunol. 1988 Jun;72(3):450–456. [PMC free article] [PubMed] [Google Scholar]
- Sammaritano L. R., Gharavi A. E., Lockshin M. D. Antiphospholipid antibody syndrome: immunologic and clinical aspects. Semin Arthritis Rheum. 1990 Oct;20(2):81–96. doi: 10.1016/0049-0172(90)90021-7. [DOI] [PubMed] [Google Scholar]
- Sammaritano L. R., Gharavi A. E., Soberano C., Levy R. A., Lockshin M. D. Phospholipid binding of antiphospholipid antibodies and placental anticoagulant protein. J Clin Immunol. 1992 Jan;12(1):27–35. doi: 10.1007/BF00918270. [DOI] [PubMed] [Google Scholar]
- Sammaritano L. R., Lockshin M. D., Gharavi A. E. Antiphospholipid antibodies differ in aPL cofactor requirement. Lupus. 1992 Feb;1(2):83–90. doi: 10.1177/096120339200100205. [DOI] [PubMed] [Google Scholar]
- Shi W., Chong B. H., Chesterman C. N. Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. Blood. 1993 Mar 1;81(5):1255–1262. [PubMed] [Google Scholar]
- Smirnov M. D., Triplett D. T., Comp P. C., Esmon N. L., Esmon C. T. On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies. J Clin Invest. 1995 Jan;95(1):309–316. doi: 10.1172/JCI117657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
- Thornhill M. H., Wellicome S. M., Mahiouz D. L., Lanchbury J. S., Kyan-Aung U., Haskard D. O. Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms. J Immunol. 1991 Jan 15;146(2):592–598. [PubMed] [Google Scholar]
- Ziegler-Heitbrock H. W., Thiel E., Fütterer A., Herzog V., Wirtz A., Riethmüller G. Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes. Int J Cancer. 1988 Mar 15;41(3):456–461. doi: 10.1002/ijc.2910410324. [DOI] [PubMed] [Google Scholar]