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DOI: 10.1160/TH09-12-0849
Phagocytosis of platelet microvesicles and β2– glycoprotein I
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.Publication History
Received:
18 December 2009
Accepted after minor revision:
31 March 2010
Publication Date:
24 November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201002/lookinside/thumbnails/10-1160-th09-12-0849-1.jpg)
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.
* These two authors contributed equally.
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