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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   *
1   Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA
,
Swapan K. Dasgupta   *
1   Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA
,
Anhquyen Le
1   Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA
,
Anthony Prakasam
1   Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA
,
Perumal Thiagarajan
1   Departments of Pathology and Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA
› Author Affiliations Financial support: This study was supported by a grant from a Merit Review Grant from Veterans Affairs Research Service and a training grant from National Institutes of Health.
Further Information

Publication History

Received: 18 December 2009

Accepted after minor revision: 31 March 2010

Publication Date:
24 November 2017 (online)

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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

* These two authors contributed equally.


 

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