Localization of β2-Glycoprotein 1 in Late Endosomes of Human Endothelial Cells

S. Dunoyer-Geindre; E. K. O. Kruithof; Galve-de B. Rochemonteix; C. Rosnoblet; J. Gruenberg; G. Reber; P. de Moerloose

doi:10.1055/s-0037-1615766

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(05): 903-907
DOI: 10.1055/s-0037-1615766

Review Article

Schattauer GmbH

Localization of β₂-Glycoprotein 1 in Late Endosomes of Human Endothelial Cells

S. Dunoyer-Geindre

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

E. K. O. Kruithof

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

Galve-de B. Rochemonteix

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

C. Rosnoblet

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

J. Gruenberg

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

G. Reber

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

,

P. de Moerloose

¹Division of Angiology and Haemostasis, University Hospital of Geneva, Biochemistry Department, University of Geneva, Switzerland

› Author Affiliations

Abstract

Summary

Antiphospholipid antibodies (APLA) are associated with thrombophilia and recurrent pregnancy loss. Different mechanisms have been proposed to explain their pathogenic effects and among them, we have previously shown that APLA accumulate in late endosomes of human umbilical vein endothelial cells (HUVEC) leading to a redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR). Because many APLA are directed towards β₂-glycoprotein 1 (β₂GP1)-phospholipid complexes, we investigated the localisation of β₂GP1 in HUVEC. By immunofluorescence analysis, using monoclonal and polyclonal anti- β₂GP1 antibodies, we detected β₂GP1 at the cell surface and in late endosomes. Incubation of HUVEC with anti- β₂GP1 antibodies resulted in antibody accumulation at the cell surface and within late endosomes and in a redistribution of the CI-M6PR from the Golgi apparatus to late endosomes. The anti- β₂GP1 antibodies remained detectable in late endosomes even after several days of incubation in antibody-free medium. The accumulation of anti- β₂GP1 antibodies in late endosomes of endothelial cells and the resulting modification of intracellular protein trafficking may contribute to the pathogenic effects of these antibodies.

Keywords

β₂-glycoprotein 1 - late endosomes - endothelial cells - anti-phospholipid antibodies

Full Text

References

References
1 Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 1999; 7: 1309-11.
2 Roubey RAS. Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum 1996; 39: 1444-56.
3 Martinuzzo ME, Forastiero RR, Carreras LO. Anti-β₂ glycoprotein 1 antibodies: detection and association with thrombosis. Br J Haematol 1995; 89: 397-402.
4 McNally T, Mackie IJ, Machin SJ, Isenberg DA. Increased levels of β_2-glycoprotein-I antigen and β₂-glycoprotein-I binding antibodies are associated with a history of thromboembolic complications in patients with SLE and primary antiphospholipid syndrome. Br J Rheumatol 1995; 34: 1031-6.
5 Alarcon-Segovia D, Mestanza M, Cabiedes Cabral A. The antiphospholipid/cofactor syndromes. A variant in patients with systemic lupus erythematosus with antibodies to β₂GP1 but no antibodies detectable in standard antiphospholipid assays. J Rheumatol 1997; 24: 1545-51.
6 Sebastiani GD, Galleazzi M, Tincani A, Piette JC, Font J, Allegri F, Mathieu A, Smolen J, de Ramon Garrido E, Fernandez-Nebro A, JedrykaGoral A, Papasteriades C, Morozzi G, Bellisai F, De Pita O, Marcolongo R. Anticardiolipin and anti-β₂GP1 antibodies in a large series of European patients with systemic lupus erythematosus. Scand J Rheumatol 1999; 28: 344-51.
7 Greco TP, Amos MD, Conti-Kelly AM, Naranjo JD, Idjo JW. Testing for the antiphospholipid syndrome : importance of IgA and anti-beta 2-glyco-protein 1. Lupus 2000; 9: 33-41.
8 Blank M, Faden D, Tincani A, Kopolovic J, Goldberg I, Gilburd B, Allegri F, Balestrieri G, Valesini G, Shoenfeld Y. Immunization with anticardiolipin cofactor (beta-2 glycoprotein-1) induces antiphospholipid syndrome in naive mice. J Autoimmun 1994; 7: 441-55.
9 Pierangeli SS, Liu SW, Anderson G, Barker JM, Harris EN. Thrombogenic properties of anti-cardiolipin antibodies induced by beta 2 glycoprotein 1 and human immunoglobulins G antiphospholipid antibodies. Circulation 1996; 94: 1746-51.
10 Garcia CO, Kanbour-Shakir A, Tang H, Molina JF, Espinoza LR, Gharavi AE. Induction of experimental antiphospholipid syndrome in PL/J mice following immunization with beta2 glycoprotein 1. Am J Reprod Immunol 1997; 37: 118-24.
11 Meroni PL, Del Papa N, Raschi P, Panzeri P, Borghi MO, Ponticelli C, Tincani A, Balestrieri G, Khamashta MA, Hughes GR, Koke T, Krilis SA. β₂-Glycoprotein I, as “cofactor” for antiphospholipid reactivity with endothelial cells. Lupus 1998; 7: S44-S7.
12 Caronti B, Calderaro C, Alessandri C, Conti F, Tinghino R, Palladini G, Valesini G. β₂-glycoprotein I (β₂-GPI) mRNA is expressed by several cell types involved in anti-phospholipid syndrome-related tissue damage. Clin Exp Immunol 1999; 115: 214-9.
13 Galve-de Rochemonteix B, Kobayashi T, Rosnoblet C, Lindsay M, Parton RG, Reber G, de Maistre E, Wahl D, Kruithof EK, Gruenberg J, de Moer-loose P. Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 563-74.
14 Regnault V, Arvieux J, Vallar L, Lecompte T. Both kinetic data and epitope mapping provide clues for understanding the anticoagulant effect of five murine monoclonal antibodies to human β₂-Glycoprotein 1. Immunology 1999; 97: 400-7.
15 Kobayashi T, Stang E, Fang KS, de Moerloose P, Parton RG, Gruenberg J. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 1998; 392: 193-7.
16 Del Papa N, Guidali L, Sala A, Buccellati C, Khamashta MA, Ichikawa K, Koike T, Balestrieri G, Tincani A, Hughes GR, Meroni PL. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-β₂-Glycoprotein I, antibodies react in vitro with endothelial cells through adherent β₂Glycoprotein I, and induce endothelial activation. Arthritis Rheum 1997; 40: 551-61.
17 Ma K, Simantov R, Zhang JC, Silverstein R, Hajjar KA, McCrae KR. High affinity binding of beta 2-glycoprotein I to human endothelial cells is mediated by annexin II. J Biol Chem 2000; 275: 15541-8.
18 Ludwig T, Munier-Lehmann H, Bauer U, Hollinshead M, Ovitt C, Lobel P, Hoflack B. Differential sorting of lysosomal enzymes in mannose 6-phosphate receptor-deficient fibroblasts. EMBO J 1994; 13: 3430-7.
19 Pohlmann R, Wendland M, Boeker C, von Figura K. The two mannose 6-phosphate receptors transport distinct complements of lysosomal proteins. J Biol Chem 1995; 270: 27311-8.
20 Dittmer F, Ulbrich EJ, Hafner A, Schmahl W, Meister T, Pohlmann R, von Figura K. Alternative mechanisms for trafficking of lysosomal enzymes in mannose 6-phosphate receptor-deficient mice are cell type-specific. J Cell Sci 1999; 112: 1591-7.
21 Kimura Y, Yokoi-Hayashi K. Polymorphonuclear leukocyte lysosomal pro-teases, cathepsins B and D affect the fibrinolytic system in human umbilical vein endothelial cells. Biochim Biophys Acta 1996; 1310: 1-4.
22 Kolpakov V, D’Adamo MC, Salvatore L, Amore C, Mironov A, Iacoviello L, Donati MB. Neutrophil derived cathepsin G induces potentially thrombogenic changes in human endothelial cells: a scanning electron microscopy study in static and dynamic conditions. Thromb Haemost 1994; 72: 140-5.
23 Chung CY, Murphy-Ullrich JE, Erickson HP. Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II. Mol Biol Cell 1996; 7: 883-92.
24 Emans N, Gorvel JP, Walter C, Gerke V, Kellner R, Griffiths G, Gruenberg J. Annexin II is a major component of fusogenic endosomal vesicles. J Cell Biol 1993; 120: 1357-69.
25 Van der Goot FG. Separation of early steps in endocytic membrane transport. Electrophoresis 1997; 18: 2689-93.
26 Alvarado-de la Barrera C, Bahena S, Llorente Luis Martinez-Castillo A, Alarc-Segovia D, Cabral AR. β₂-Glycoprotein-1 mRNA transcripts are expressed by hepatocytes but not by resting or activated human endothelial cells. Thromb Res 1998; 90: 239-43.