Vimentin Exposed on Activated Platelets and Platelet Microparticles Localizes Vitronectin and Plasminogen Activator Inhibitor Complexes on Their Surface

Podor, Thomas J.; Singh, Davindra; Chindemi, Paul A.; Foulon, D; McKelvie, Robert S.; Weitz, Jeffrey I.; Austin, Richard C.; Boudreau, Ghislain; Davies, R.C.

doi:10.1074/jbc.m109675200

Cited by 114 publications

(98 citation statements)

References 65 publications

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“…Consistent with its polarized detection on the luminal side of endothelial cells in tissue sections, PAL-E-reactive vimentin is also readily detected in human circulating blood. This finding is likely to explain a recent report of vimentin associated with vitronectin and plasminogen activator inhibitor on the surface of activated platelets (20), since platelets internalize many circulating proteins, including vitronectin, that are subsequently released during platelet granule secretion after platelet activation. Thus, our findings and previous work characterizing the PAL-E antibody suggest that it selectively recognizes a secreted form of vimentin produced by blood vascular endothelial cells.…”

Section: Vol 24 2004 Pal-e Identifies Vimentin From Blood Endothelimentioning

confidence: 56%

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

deWaal²,

Mor‐Vaknin

et al. 2004

Molecular and Cellular Biology

104

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During mammalian vascular development, endothelial cells form a complex array of vessels that differ markedly in structure and function, but the molecular basis for this vascular complexity is poorly understood. Recent insights into endothelial diversity have come from the identification of molecular markers expressed on distinct endothelial cell populations. One such marker, the PAL-E antibody, has been used for almost 20 years to distinguish blood and lymphatic vessels, but the identity of the protein recognized by PAL-E has been unknown. In the present study we have used protein purification and tandem mass spectrometry analysis of tryptic peptides to identify the PAL-E antigen as a secreted form of vimentin. Vimentin has been well characterized as an intracellular intermediate filament protein expressed broadly in mesenchymal cells. In contrast, PAL-E-reactive vimentin is secreted extracellularly, its synthesis is restricted to a distinct population of blood endothelial cells and activated macrophages, and PAL-E-reactive vimentin is found in circulating human blood. PAL-E-reactive vimentin does not arise from an endothelial cell-specific mRNA transcript but is the product of cell-specific posttranslational modification. The PAL-E antibody therefore defines secretion of vimentin as a molecular distinction among endothelial cells and exposes a novel, extracellular role for vimentin in the blood vasculature.

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Section: Vol 24 2004 Pal-e Identifies Vimentin From Blood Endothelimentioning

confidence: 56%

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

deWaal²,

Mor‐Vaknin

et al. 2004

Molecular and Cellular Biology

104

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“…Indeed, since platelets bind plasminogen, [36][37][38] platelet microparticles may be a source of substrate for enhanced fibrinolysis by single-chain uPA 39 via a fibrinolytic crosstalk mechanism we demonstrated recently. 11 However, active PAI-1/vitronectin complexes present in platelets 40 and active PAI-1 detected in platelet microparticles as shown in this study, may modulate this fibrinolytic activity. Given that both platelet and erythrocyte microparticle subpopulations account for the bulk of circulating microparticles, 13 it was relevant to demonstrate the effect of their depletion from the pool of microparticles isolated from plasma.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 88%

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundWe recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and MethodsCirculating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. ResultsCirculating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. ConclusionsEndothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium.Key words: fibrinolytic microparticles, plasmin, plasminogen, uPA; tPA. Plawinski L, Robert S, Doeuvre L, Sabatier F, Martinez de Lizarrondo S, Mezzapesa A, Anfosso F, Leroyer AS, Poullin P, Jourde N, Njock M-S, Boulanger CM, Anglés-Cano E, and Dignat-George F. Leukocyte-and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica 2012;97(12):1864-1872. doi:10.3324/haematol.2012 This is an open-access paper. Citation: Lacroix R, Leukocyte-and endothelial-derived microparticles: a circulating source for fibrinolysis ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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“…76 Besides their procoagulant activity, MPs may play a regulatory role in vascular remodeling and fibrinolysis, which may ultimately have therapeutic implications. In this regard, Podor et al 111 have demonstrated that the vimentin-dependent localization of active plasminogen activator inhibitor-1 on the surface of activated platelets and platelet-derived MPs is suggestive of an intricate role played by MPs in the context of atherothrombosis. Of note, endothelial MPs also support plasmin generation by expressing the urokinase-type plasminogen activator and its receptor, enabling urokinase-type plasminogen activator-driven fibrinolytic cross-talk in situ.…”

Section: Toward a Pharmacological Control Of Ps Exposure And Microparmentioning

confidence: 99%

Cellular Mechanisms Underlying the Formation of Circulating Microparticles

Morel

Jesel

Freyssinet

et al. 2011

ATVB

467

405

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Abstract-Microparticles (MPs) derived from platelets, monocytes, endothelial cells, red blood cells, and granulocytes may be detected in low concentrations in normal plasma and at increased levels in atherothrombotic cardiovascular diseases. The elucidation of the cellular mechanisms underlying the generation of circulating MPs is crucial for improving our understanding of their pathophysiological role in health and disease. The flopping of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the key event that will ultimately lead to the shedding of procoagulant MPs from activated or apoptotic cells. Research over the last few years has revealed important roles for calcium-, mitochondrial-, and caspase-dependent mechanisms leading to PS exposure. The study of Scott cells has unraveled different molecular mechanisms that may contribute to fine-tuning of PS exposure and MP release in response to a variety of specific stimuli. The pharmacological modulation of MP release may have a substantial therapeutic impact in the management of atherothrombotic vascular disorders. Because PS exposure is a key feature in pathological processes different from hemostasis and thrombosis, the most important obstacle in the field of MP-modulating drugs seems to be carefully targeting MP release to relevant cell types at an optimal level, so as to achieve a beneficial action and limit possible adverse effects. (Arterioscler Thromb Vasc Biol. 2011;31:15-26.)

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Vimentin Exposed on Activated Platelets and Platelet Microparticles Localizes Vitronectin and Plasminogen Activator Inhibitor Complexes on Their Surface

Cited by 114 publications

References 65 publications

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

The Endothelial Cell-Specific Antibody PAL-E Identifies a Secreted Form of Vimentin in the Blood Vasculature

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

Cellular Mechanisms Underlying the Formation of Circulating Microparticles

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