Internalization of microparticles by endothelial cells promotes platelet/endothelial cell interaction under flow

Background: Microparticles (MPs) released by activated or apoptotic cells increase in number in the blood of subjects with vascular or metabolic diseases and may contribute to thrombotic complications. Objectives: In this study, we investigated whether MPs promoted platelet recruitment to endothelia...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2010-12, Vol.8 (12), p.2810-2819
Main Authors: TERRISSE, A. D., PUECH, N., ALLART, S., GOURDY, P., XUEREB, J. M., PAYRASTRE, B., SIÉ, P.
Format: Article
Language:English
Subjects:
Adult
Blood Platelets - cytology
Case-Control Studies
Cells, Cultured
diabetes
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - pathology
Endocytosis
endothelial cells
Endothelium, Vascular - cytology
Humans
microparticles
Microscopy, Confocal
Microspheres
Middle Aged
P-Selectin - metabolism
Platelet Glycoprotein GPIb-IX Complex - metabolism
platelets
von Willebrand factor
von Willebrand Factor - metabolism
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Summary:Background: Microparticles (MPs) released by activated or apoptotic cells increase in number in the blood of subjects with vascular or metabolic diseases and may contribute to thrombotic complications. Objectives: In this study, we investigated whether MPs promoted platelet recruitment to endothelial cells in flow conditions, and by which mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) grown in microslide perfusion chambers were exposed to MPs prepared in vitro from HUVECs, monocytes or platelets. Results: Videomicroscopy of DIOC‐labelled blood perfused at arterial rate on human umbilical vein ECs demonstrated that, irrespective of their cell origin, MPs promoted the formation of platelet strings at the surface of HUVECs. This platelet/endothelial cell interaction was dependent on von Willebrand factor (VWF) expression at the HUVEC surface and involved Glycoprotein Ib and P‐selectin. Interestingly, HUVECs internalized MPs within a few hours through a process involving anionic phospholipids, lactadherin and αvβ3 integrin. This uptake generated the production of reactive oxygen species via the xanthine/xanthine oxidase system (inhibited by allopurinol and the ROCK inhibitor Y‐27632) and the NADPH oxidase (inhibited by SOD). Reactive oxygen species appeared essential for VWF expression at the endothelial cell surface and subsequent platelet/endothelial cell interaction under flow. The pathophysiological relevance of this process is underlined by the fact that circulating MPs from Type I diabetic patients induced platelet/endothelial cell interaction under flow, with an intensity correlated with the severity of the vasculopathy.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2010.04088.x