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      Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

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          Abstract

          Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS +/PS ), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis.

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          CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.

          CD40 ligand (CD40L, CD154), a transmembrane protein structurally related to the cytokine TNF-alpha, was originally identified on stimulated CD4+ T cells, and later on stimulated mast cells and basophils. Interaction of CD40L on T cells with CD40 on B cells is of paramount importance for the development and function of the humoral immune system. CD40 is not only constitutively present on B cells, but it is also found on monocytes, macrophages and endothelial cells, suggesting that CD40L has a broader function in vivo. We now report that platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo. Like TNF-alpha and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby generating signals for the recruitment and extravasation of leukocytes at the site of injury. Our results indicate that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.
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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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              Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop.

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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                25 October 2016
                2016
                : 6
                : 36025
                Affiliations
                [1 ]Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital , SE-171 76 Stockholm, Sweden
                [2 ]Department of Clinical Chemistry and Pharmacology, Akademiska Hospital , SE-751 85 Uppsala, Sweden
                [3 ]Department of Medicine, Duke University Medical Center; Medical Research Service, Durham VA Hospital , NC, USA
                [4 ]Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Division of Cardiovascular Medicine , Stockholm, Sweden
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep36025
                10.1038/srep36025
                5078765
                27777414
                c57fb0c1-4225-497d-a345-1ddcd46b3522
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 24 August 2016
                : 10 October 2016
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