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      The role of platelets in the recruitment of leukocytes during vascular disease

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          Abstract

          Besides their role in the formation of thrombus during haemostasis, it is becoming clear that platelets contribute to a number of other processes within the vasculature. Indeed, the integrated function of the thrombotic and inflammatory systems, which results in platelet-mediated recruitment of leukocytes, is now considered to be of great importance in the propagation, progression and pathogenesis of atherosclerotic disease of the arteries. There are three scenarios by which platelets can interact with leukocytes: (1) during haemostasis, when platelets adhere to and are activated on sub-endothelial matrix proteins exposed by vascular damage and then recruit leukocytes to a growing thrombus. (2) Platelets adhere to and are activated on stimulated endothelial cells and then bridge blood borne leukocytes to the vessel wall and. (3) Adhesion between platelets and leukocytes occurs in the blood leading to formation of heterotypic aggregates prior to contact with endothelial cells. In the following review we will not discuss leukocyte recruitment during haemostasis, as this represents a physiological response to tissue trauma that can progress, at least in its early stages, in the absence of inflammation. Rather we will deal with scenarios 2 and 3, as these pathways of platelet–leukocyte interactions are important during inflammation and in chronic inflammatory diseases such as atherosclerosis. Indeed, these interactions mean that leukocytes possess means of adhesion to the vessel wall under conditions that may not normally be permissive of leukocyte–endothelial cell adhesion, meaning that the disease process may be able to bypass the regulatory pathways which would ordinarily moderate the inflammatory response.

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          Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.

          We have identified new activating receptors of the Ig superfamily expressed on human myeloid cells, called TREM (triggering receptor expressed on myeloid cells). TREM-1 is selectively expressed on blood neutrophils and a subset of monocytes and is up-regulated by bacterial LPS. Engagement of TREM-1 triggers secretion of IL-8, monocyte chemotactic protein-1, and TNF-alpha and induces neutrophil degranulation. Intracellularly, TREM-1 induces Ca2+ mobilization and tyrosine phosphorylation of extracellular signal-related kinase 1 (ERK1), ERK2 and phospholipase C-gamma. To mediate activation, TREM-1 associates with the transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation of neutrophil and monocytes, and may have a predominant role in inflammatory responses.
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            Resolution of inflammation: state of the art, definitions and terms.

            A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution.
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              Microparticles in hemostasis and thrombosis.

              Blood contains microparticles (MPs) derived from a variety of cell types, including platelets, monocytes, and endothelial cells. In addition, tumors release MPs into the circulation. MPs are formed from membrane blebs that are released from the cell surface by proteolytic cleavage of the cytoskeleton. All MPs are procoagulant because they provide a membrane surface for the assembly of components of the coagulation protease cascade. Importantly, procoagulant activity is increased by the presence of anionic phospholipids, particularly phosphatidylserine (PS), and the procoagulant protein tissue factor (TF), which is the major cellular activator of the clotting cascade. High levels of platelet-derived PS(+) MPs are present in healthy individuals, whereas the number of TF(+), PS(+) MPs is undetectable or very low. However, levels of PS(+), TF(+) MPs are readily detected in a variety of diseases, and monocytes appear to be the primary cellular source. In cancer, PS(+), TF(+) MPs are derived from tumors and may serve as a useful biomarker to identify patients at risk for venous thrombosis. This review will summarize our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis.
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                Author and article information

                Journal
                Platelets
                Platelets
                IPLT
                iplt20
                Platelets
                Informa Healthcare
                0953-7104
                1369-1635
                18 August 2015
                21 July 2015
                : 26
                : 6
                : 507-520
                Affiliations
                [ a ]Centre for Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, The University of Birmingham , Birmingham, UK
                [ b ]Universite de Montreal, Faculte de Pharmacie , Montreal, Quebec, Canada
                Author notes
                Correspondance: G. Ed Rainger, Centre for Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, The University of Birmingham , Birmingham B15 2TT, UK. Tel: +44 (0)121 414 4040. Fax: +44 (0)121 4146919. E-mail: g.e.rainger@ 123456bham.ac.uk
                Article
                1064881
                10.3109/09537104.2015.1064881
                4673595
                26196409
                42714dac-e1f8-445f-b5b8-b66ad858fb0d
                © 2015 The Author(s). Published with license by Informa UK Ltd.

                © G. Ed Rainger, Myriam Chimen, Matthew J. Harrison, Clara M. Yates, Paul Harrison, Stephen P. Watson, Marie Lordkipanidzé, and Gerard B. Nash

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 31 March 2015
                : 18 May 2015
                : 18 June 2015
                Page count
                Pages: 14
                Categories
                Methods Paper

                adhesion,inflammation,leukocytes,platelets,vascular disease
                adhesion, inflammation, leukocytes, platelets, vascular disease

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