Page 88 - Haematologica May 2020

Ferrata Storti Foundation
Haematologica 2020 Volume 105(5):1248-1261
Monocyte Biology & its Disorders
Appropriation of GPIbα from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation
Myriam Chimen,1,2 Aigli Evryviadou,1 Clare L. Box,1 Matthew J. Harrison,1 Jon Hazeldine,2 Lea H. Dib,1 Sahithi J. Kuravi,1 Holly Payne,1 Joshua M.J. Price,2 Dean Kavanagh,1 Asif J. Iqbal,1 Sian Lax,1 Neena Kalia,1 Alex Brill,1,3,4 Steve G. Thomas,1,3 Antonio Belli,2 Nicholas Crombie,2 Rachel A. Adams,5 Shelley-Ann Evans,5 Hans Deckmyn,6 Janet M. Lord,2 Paul Harrison,2 Steve P. Watson,1,3 Gerard B. Nash1 and G. Ed Rainger1
1Institute of Cardiovascular Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK; 2NIHR Surgical Reconstruction and Microbiology Research Centre, Institute of Inflammation and Ageing, Birmingham University Medical School, Birmingham, UK;3Centre of Membrane Proteins and Receptors, University of Birmingham and Nottingham, The Midlands, UK; 4Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 5Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK and 6Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
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 vesicles 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 bind- ing of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to 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-/- 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 trau- ma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicles transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is like- ly to be pathogenic.
Introduction
The recruitment of leukocytes during inflammation occurs in the haemodynami- cally permissive environment of the post capillary venules. In this environment, vas- cular endothelial cells responding to pro-inflammatory mediators such as cytokines express adhesion receptors and activating stimuli such as chemokines, which ensure efficient and localised trafficking of leukocytes into the affected tissues.1-4 It has become clear more recently that in pathological situations, platelets can also play a
Correspondence:
MYRIAM CHIMEN
chimenm@bham.ac.uk
Received: December 21, 2018. Accepted: August 23, 2019. Pre-published: August 29, 2019.
doi:10.3324/haematol.2018.215145
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/5/1248
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