Phagocytosis of platelet microvesicles and β2– glycoprotein I

Hanan Abdel-Monem; Swapan K. Dasgupta; Anhquyen Le; Anthony Prakasam; Perumal Thiagarajan

doi:10.1160/TH09-12-0849

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 104(02): 335-341
DOI: 10.1160/TH09-12-0849

Endothelium and Vascular Development

Schattauer GmbH

Phagocytosis of platelet microvesicles and β2– glycoprotein I

Hanan Abdel-Monem^*

¹Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA

,

Swapan K. Dasgupta^*

¹Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA

,

Anhquyen Le

¹Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA

,

Anthony Prakasam

¹Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA

,

Perumal Thiagarajan

¹Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA

› Institutsangaben

Abstract

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Summary

The majority of the antiphospholipid antibodies, present in patients with antiphospholipid syndrome, are directed against conformational epitopes in β2-glycoprotein I. β2-glycoprotein I is an anionic phospholipid- binding 50-kDa plasma protein whose physiological role is not clear. Here we investigate the role of β2-glycoprotein I in the phagocytosis of phosphatidylserine-expressing platelet microvesicles and the effect of autoantibodies to β2-glycoprotein I on this process. We labelled the glycans of β2-glycoprotein I with BODIPY (4,4-difluoro- 4-bora-3a,4a-diaza-s-indacene)-hydrazide without affecting its phospholipid binding capacity. BODIPY-β2-glycoprotein I bound to platelet microvesicles in a concentration-dependent manner and promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at ∼10 μg/ml. β2-glycoprotein I-stimulated phagocytosis was inhibited by annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified β2-glycoprotein I-dependent antiphospholipid antibodies from five patients with antiphospholipid syndrome inhibited the phagocytosis in a concentration- dependent manner. These studies suggest that the binding of β2-glycoprotein I to phosphatidylserine-expressing procoagulant platelet microvesicles may promote their clearance by phagocytosis and autoantibodies to β2-glycoprotein I may inhibit this process to induce a procoagulant state.

Keywords

β2-glycoprotein I - antiphospholipid antibodies - platelet microvesicles - phagocytosis

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Referenzen

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