Download PDF
Thromb Haemost 2001; 86(05): 1257-1263
DOI: 10.1055/s-0037-1616059
Review Article
Schattauer GmbH

Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

Attilio Bondanza
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Angelo A. Manfredi
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Valérie S. Zimmermann
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Matteo Iannacone
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Angela Tincani
2   Clinical Immunology Unit, Spedali Civili, Brescia, Italy
,
Genesio Balestrieri
2   Clinical Immunology Unit, Spedali Civili, Brescia, Italy
,
Maria Grazia Sabbadini
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Patrizia Rovere Querini
1   Immunopathology Unit-Cancer Immunotherapy and Gene Therapy Programme, Istituto Scientifico H S. Raffaele, Milano, Italy
› Author Affiliations
Further Information

Publication History

Received 01 June 2001

Accepted after revision 31 July 2001

Publication Date:
13 December 2017 (online)

   Permissions and Reprints

Summary

Scavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

Keywords

Antiphospholipid antibodies - platelets - macrophages - dendritic cells - tumor necrosis factor-α
 

  • References

  • 1 Baker GR, Levin J. Transient thrombocytopenia produced by administration of macrophage colony-stimulating factor: investigations of the mechanism. Blood 1998; 91: 89-99.
    CrossrefPubMedSearch in Google Scholar
  • 2 Brown SB, Clarke MC, Magowan L, Sanderson H, Savill J. Constitutive death of platelets leading to scavenger receptor-mediated phagocytosis. A caspase-independent cell clearance program. J Biol Chem 2000; 190: 5987-96.
    PubMedSearch in Google Scholar
  • 3 Escolar G, White JG. Changes in glycoprotein expression after platelet activation: differences between in vitro and in vivo studies. Thromb Haemost 2000; 83: 371-86.
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Thiagarajan P, Tait JF. Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J Biol Chem 1990; 265: 17420-3.
    PubMedSearch in Google Scholar
  • 5 Stuart MC, Bevers EM, Comfurius P, Zwaal RF, Reutelingsperger CP, Frederik PM. Ultrastructural detection of surface exposed phosphatidylserine on activated blood platelets. Thromb Haemost 1995; 74: 1145-51.
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Pereira J, Palomo I, Ocqueteau M, Soto M, Aranda E, Mezzano D. Platelet aging in vivo is associated with loss of membrane phospholipid asymmetry. Thromb Haemost 1999; 82: 1318-21.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Fadok VA, Bratton D, Courtney Frasch L, Warner ML, Henson PM. The role of phosphatidylserine in the recognition of apoptotic cells by phagocytes. Cell Death Diff 1998; 5: 551-62.
    CrossrefPubMedSearch in Google Scholar
  • 8 Bevers EM, Comfurius P, Dekkers DW, Harmsma M, Zwaal RF. Transmembrane phospholipid distribution in blood cells: control mechanisms and pathophysiological significance. Biol Chem 1998; 379: 973-86.
    PubMedSearch in Google Scholar
  • 9 Rand JH, Wu XX. Antibody-mediated disruption of the annexin-V anti-thrombotic shield: a new mechanism for thrombosis in the antiphospholipid syndrome. Thromb Haemost 1999; 82: 649-55.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Shi W, Chong BH, Chesterman CN. Beta 2-glycoprotein I is a requirement for anticardiolipin binding to activated platelets: differences with lupus anticoagulants. Blood 1993; 81: 1255-62.
    PubMedSearch in Google Scholar
  • 11 Vazquez-Mellado J, Llorente L, Richaud-Patin Y, Alarcon-Segovia D. Exposure of anionic phospholipids upon platelet activation permits binding of beta 2 glycoprotein I and through it that of IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal subjects. J Autoimmun 1994; 7: 335-48.
    CrossrefPubMedSearch in Google Scholar
  • 12 Roubey RA. Immunology of the antiphospholipid syndrome: antibodies, antigens, and autoimmune response. Thromb Haemost 1999; 82: 656-61.
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Lackner KJ, von Landenberg C, Barlage S, Schmitz G. Analysis of prothrombotic effects of two human monoclonal IgG antiphospholipid antibodies of apparently similar specificity. Thromb Haemost 2000; 83: 583-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Guerin J, Sim R, Yu BB, Ferluga J, Feighery C, Jackson J. Heterogeneous recognition of beta 2-glycoprotein I by antibodies from antiphospholipid syndrome patients. Thromb Haemost 2000; 84: 374-80.
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Pierangeli SS, Liu X, Espinola R, Olee T, Zhu M, Harris NE, Chen PP. Functional analyses of patient-derived IgG monoclonal anticardiolipin antibodies using in vivo thrombosis and in vivo microcirculation models. Thromb Haemost 2000; 84: 388-95.
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Bondanza A, Sabbadini MG, Pellegatta F, Zimmermann VS, Tincani A, Balestrieri G, Manfredi AA, Rovere P. Anti-beta2 glycoprotein I antibodies prevent the de-activation of platelets and sustain their phagocytic clearance. J Autoimmun 2000; 15: 469-77.
    CrossrefPubMedSearch in Google Scholar
  • 17 Dombroski D, Balasubramanian K, Schroit AJ. Phosphatidylserine expression on cell surfaces promotes antibody-dependent aggregation and thrombosis in beta2-glycoprotein I-immune mice. J Autoimmun 2000; 14: 221-9.
    CrossrefPubMedSearch in Google Scholar
  • 18 Salemink I, Blezer R, Willems GM, Galli M, Bevers E, Lindhout T. Antibodies to beta2-glycoprotein I associated with antiphospholipid syndrome suppress the inhibitory activity of tissue factor pathway inhibitor. Thromb Haemost 2000; 84: 653-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Cuadrado MJ, Lopez-Pedrera C, Khamashta MA, Camps MT, Tinahones F, Torres A, Hughes GR, Velasco F. Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression. Arthritis Rheum 1997; 40: 834-41.
    CrossrefPubMedSearch in Google Scholar
  • 20 Bertolaccini ML, Atsumi T, Lanchbury JS, Caliz AR, Katsumata K, Vaughan RW, Kondeatis E, Khamashta MA, Koike T, Hughes GR. Plasma tumor necrosis factor alpha levels and the -238*A promoter polymorphism in patients with antiphospholipid syndrome. Thromb Haemost 2001; 85: 198-203.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Science 1998; 392: 245-52.
    PubMedSearch in Google Scholar
  • 22 Tincani A, Spatola L, Prati E, Allegri F, Ferremi P, Cattaneo R, Meroni PL, Balestrieri G. The anti-beta2-glycoprotein I activity in human antiphospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2 glycoprotein I and preserved during species evolution. J Immunol 1996; 157: 5732-8.
    PubMedSearch in Google Scholar
  • 23 Manfredi AA, Rovere P, Heltai S, Galati G, Nebbia G, Tincani A, Balestrieri G, Sabbadini MG. Apoptotic cell clearance in Systemic Lupus Erythematosus: II. Role for the beta2-glycoprotein I. Arthritis Rheum 1998; 41: 215-23.
    CrossrefPubMedSearch in Google Scholar
  • 24 Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1998; 25: 1271-7.
    PubMedSearch in Google Scholar
  • 25 Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Dersken R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-11.
    CrossrefPubMedSearch in Google Scholar
  • 26 Bondanza A, Rovere P, Borri A, Caremoli ER, Guidetti A, Citterio G, Consogno G, Zimmermann VS, Rugarli C, Manfredi AA. Cytokine secretion associated with the clearance of apoptotic bodies in renal cell carcinoma patients. Int J Cancer 2001; 91: 713-7.
    CrossrefPubMedSearch in Google Scholar
  • 27 Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony stimulating factor plus interleukin 4 and down regulated by tumor necrosis factor-. J Exp Med 1994; 179: 1109-18.
    CrossrefPubMedSearch in Google Scholar
  • 28 La Rosa L, Meroni PL, Tincani A, Balestrieri G, Faden D, Lojacono A, Morassi L, Brocchi E, Sammaritano L, Lockshin M. Beta 2 glycoprotein I and placental anticoagulant protein I in placentae from patients with antiphospholipid syndrome. J Rheumatol 1994; 21: 1684-93.
    PubMedSearch in Google Scholar
  • 29 Aas KA, Gardner FH. Survival of blood platelets labeled with chromium. J Clin Invest 1958; 37: 1257-66.
    CrossrefPubMedSearch in Google Scholar
  • 30 Kornberg A, Blank M, Kaufman S, Shoenfeld Y. Induction of tissue factor-like activity in monocytes by anticardiolipin antibodies. J Immunol 1994; 153: 1328-32.
    PubMedSearch in Google Scholar
  • 31 Amengual O, Atsumi T, Khamashta MA, Hughes GR. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 1998; 79: 276-81.
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Reverter JC, Tassies D, Font J, Khamashta MA, Ichikawa K, Cervera R, Escolar G, Hughes GR, Ingelmo M, Ordinas A. Effects of human monoclonal anticardiolipin antibodies on platelet function and on tissue factor expression on monocytes. Arthritis Rheum 1998; 41: 1420-7.
    CrossrefPubMedSearch in Google Scholar
  • 33 Hoffman M, Monroe DM, Roubey RA. Links between the immune and coagulation systems: how do “antiphospholipid antibodies” cause thrombosis?. Immunol Res 2001; 22: 191-7.
    PubMedSearch in Google Scholar
  • 34 Dobado-Berrios PM, Lopez-Pedrera C, Velasco F, Aguirre MA, Torres A, Cuadrado MJ. Increased levels of tissue factor mRNA in mononuclear blood cells of patients with primary antiphospholipid syndrome. Thromb Haemost 1999; 82: 1578-82.
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 Speiser W, Kapiotis S, Kopp CW, Simonitsch I, Jilma B, Jansen B, Exner M, Chott A. Effect of intradermal tumor necrosis factor-alpha-induced inflammation on coagulation factors in dermal vessel endothelium. An in vivo study of human skin biopsies. Thromb Haemost 2001; 85: 362-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Albert ML, Kim JI, Birge RB. Alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells. Nat Cell Biol 2000; 2: 899-905.
    CrossrefPubMedSearch in Google Scholar
  • 37 Bang KW, Speck ER, Blanchette VS, Freedman J, Semple JW. Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens. Blood 2000; 95: 1735-42.
    PubMedSearch in Google Scholar
  • 38 Rovere P, Sabbadini MG, Vallinoto C, Fascio U, Rescigno M, Crosti M, Ricciardi-Castagnoli P, Balestrieri G, Tincani A, Manfredi AA. Dendritic cell presentation of antigens from apoptotic cells in a pro-inflammatory context: role of opsonizing anti-beta 2 glycoprotein I antibodies. Arthritis Rheum 1999; 42: 1412-20.
    CrossrefPubMedSearch in Google Scholar
  • 39 Rovere P, Sabbadini MG, Bondanza A, Zimmermann VS, Fazzini F, Rugarli C, Manfredi AA. Remnants of suicidal cells fostering systemic autoaggression: apoptosis in the origin and maintenance of autoimmunity. Arthritis Rheum 2000; 43: 1663-72.
    CrossrefPubMedSearch in Google Scholar