Evidence for Anticoagulant Activity and β2-GPI Accumulation in Late Endosomes of Endothelial Cells Induced by Anti-LBPA Antibodies

M. Sorice; D. Ferro; R. Misasi; V. Pittoni; A. Longo; A. Circella; T. Garofalo; R. Gradini; F. Violi; J. Gruenberg; G. Valesini

doi:10.1055/s-0037-1613073

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(04): 735-741
DOI: 10.1055/s-0037-1613073

Review Article

Schattauer GmbH

Evidence for Anticoagulant Activity and β₂-GPI Accumulation in Late Endosomes of Endothelial Cells Induced by Anti-LBPA Antibodies

Authors

M. Sorice

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
D. Ferro

²Clinica Medica I, Università “La Sapienza”, Roma, Italy
R. Misasi

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
V. Pittoni

³Cattedra di Reumatologia, Università “La Sapienza”, Roma, Italy
A. Longo

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
A. Circella

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
T. Garofalo

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
R. Gradini

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
F. Violi

²Clinica Medica I, Università “La Sapienza”, Roma, Italy
J. Gruenberg

⁴Biochemistry Department, University of Geneva, Switzerland
G. Valesini

¹Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy

Abstract

Summary

This investigation was undertaken to test whether anti-LBPA antibodies and IgG from patients with APS interfere with intracellular β₂GPI distribution in EAhy926 endothelial cells and with the coagulation system. Cell incubation with anti-LBPA MoAb or with patients’ IgG resulted in antibody binding to late endosomes and caused β₂GPI redistribution and accumulation within perinuclear vesicular structures reminiscent of late endosomes. This finding suggests that aPl may contribute to the pathogenic mechanisms of APS by modifying the intracellular traffic of proteins, by interactions between aPl and LBPA, β₂GPI and/or LBPA- β₂GPI complexes. The anticoagulant activity of anti-LBPA MoAb was analyzed in a sensitized activated partial thromboplastin time (aPTT) system and in a dilute Russell’s viper venom time (dRVVT). A significant, concentration-dependent effect of the antibody on both aPTT and dRVVT prolongation was found. These observations suggest that LBPA is an important lipid target for aPl with potential functional implications for the immunopathogenesis of APS.

Keywords

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

Volltext

Referenzen

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