Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation

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@article{b811684cdd2942a3b99b86fa8939a75b,
title = "Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation",
abstract = "Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicle which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to the monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE knockout model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicle transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic.",
keywords = "Granulocytes, Monocytes, Macrophages, Vascular Wall Biology and Platelet Adhesion, platelets, Atherosclerosis, Thrombo-Inflammation",
author = "Myriam Chimen and Aigli Evryviadou and Box, {Clare L} and Harrison, {Matthew J} and Jon Hazeldine and Dib, {Lea H} and Kuravi, {Sahithi J} and Holly Payne and Price, {Joshua M J} and Dean Kavanagh and Iqbal, {Asif J} and Sian Lax and Neena Kalia and Alexander Brill and Thomas, {Steven G} and Antonio Belli and Nicholas Crombie and Adams, {Rachel A} and Shelley-Ann Evans and Hans Deckmyn and Lord, {Janet M} and Paul Harrison and Watson, {Steve P} and Nash, {Gerard B} and Rainger, {G Ed}",
note = "Copyright {\circledC} 2019, Ferrata Storti Foundation.",
year = "2019",
month = "8",
day = "23",
doi = "10.3324/haematol.2018.215145",
language = "English",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",

}

RIS

TY - JOUR

T1 - Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation

AU - Chimen, Myriam

AU - Evryviadou, Aigli

AU - Box, Clare L

AU - Harrison, Matthew J

AU - Hazeldine, Jon

AU - Dib, Lea H

AU - Kuravi, Sahithi J

AU - Payne, Holly

AU - Price, Joshua M J

AU - Kavanagh, Dean

AU - Iqbal, Asif J

AU - Lax, Sian

AU - Kalia, Neena

AU - Brill, Alexander

AU - Thomas, Steven G

AU - Belli, Antonio

AU - Crombie, Nicholas

AU - Adams, Rachel A

AU - Evans, Shelley-Ann

AU - Deckmyn, Hans

AU - Lord, Janet M

AU - Harrison, Paul

AU - Watson, Steve P

AU - Nash, Gerard B

AU - Rainger, G Ed

N1 - Copyright © 2019, Ferrata Storti Foundation.

PY - 2019/8/23

Y1 - 2019/8/23

N2 - Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicle which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to the monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE knockout model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicle transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic.

AB - Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicle which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to the monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE knockout model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicle transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic.

KW - Granulocytes

KW - Monocytes

KW - Macrophages

KW - Vascular Wall Biology and Platelet Adhesion

KW - platelets

KW - Atherosclerosis

KW - Thrombo-Inflammation

U2 - 10.3324/haematol.2018.215145

DO - 10.3324/haematol.2018.215145

M3 - Article

C2 - 31467123

JO - Haematologica

JF - Haematologica

SN - 0390-6078

ER -