Functional Analyses of Patient-derived IgG Monoclonal Anticardiolipin Antibodies Using In Vivo Thrombosis and In Vivo Microcirculation Models

Silvia S. Pierangeli; Xiaowei Liu; Ricardo Espinola; Tsawei Olee; Min Zhu; Nigel E. Harris; Pojen P. Chen

doi:10.1055/s-0037-1607384

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(03): 388-395
DOI: 10.1055/s-0037-1607384

Thromb Haemost

Schattauer GmbH

Functional Analyses of Patient-derived IgG Monoclonal Anticardiolipin Antibodies Using In Vivo Thrombosis and In Vivo Microcirculation Models

Silvia S. Pierangeli

¹Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

,

Xiaowei Liu

¹Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

,

Ricardo Espinola

¹Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

,

Tsawei Olee

²Department of Medicine, University of California at San Diego, La Jolla, Ca, USA

,

Min Zhu

³Department of Medicine, Division of Rheumatology, University of California at Los Angeles, Los Angeles, Ca, USA

,

Nigel E. Harris

⁴Department of Internal Medicine and Dean and Senior VP of Academic Affairs, Morehouse School of Medicine, Atlanta, GA, USA

,

Pojen P. Chen

³Department of Medicine, Division of Rheumatology, University of California at Los Angeles, Los Angeles, Ca, USA

› Author Affiliations

Abstract

Summary

Antiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelial cell (EC) function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. It has been proposed that aPL may affect EC cell function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. This study proposes to test the hypotheses that some IgG anticardiolipins (IgG aCL) with thrombogenic properties in mice, exert their effects through activation of endothelium. We studied seven patient-derived monoclonal aCL for their thrombogenic properties in an in vivo pinch-induced thrombosis model, and their functional activities in activating EC by analyzing in vivo leukocyte adhesion to endothelium in microcirculation in venules in exposed murine cremaster muscle and in vitro adhesion molecule expression in cultured EC. The binding of the monoclonal aCL to EC was also tested. In addition to the previous identified thrombogenic IS2, four of the five new more IgG monoclonal aCL (from two patients) were found to be thrombogenic. Of these five thrombogenic aCL, three caused more in vivo leukocyte adhesion to EC in microcirculation, as compared to that induced by the H2 control human monoclonal IgG, and enhanced expression of adhesion molecules (particularly VCAM-1) on cultured EC. These data show that about 2/3 patientderived IgG monoclonal aCL are thrombogenic and suggest that some thrombogenic IgG aCL exert their effects through activating EC.

Key words

Antiphospholipid antibodies/syndrome - thrombosis - endothelial cell activation

Full Text

References

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