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      The Platelet Response to Tissue Injury

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          Abstract

          In recent years, various studies have increasingly explained platelet functions not only in their central role as a regulator in cellular hemostasis and coagulation. In fact, there is growing evidence that under specific conditions, platelets act as a mediator between the vascular system, hemostasis, and the immune system. Therefore, they are essential in many processes involved in tissue remodeling and tissue reorganization after injury or inflammatory responses. These processes include the promotion of inflammatory processes, the contribution to innate and adaptive immune responses during bacterial and viral infections, the modulation of angiogenesis, and the regulation of cell apoptosis in steady-state tissue homeostasis or after tissue breakdown. All in all platelets may contribute to the control of tissue homeostasis much more than generally assumed. This review summarizes the current knowledge of platelets as part of the tissue remodeling network and seeks to provide possible translational implications for clinical therapy.

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          Most cited references163

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          Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.

          It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.
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            Pericyte loss and microaneurysm formation in PDGF-B-deficient mice.

            Platelet-derived growth factor (PDGF)-B-deficient mouse embryos were found to lack microvascular pericytes, which normally form part of the capillary wall, and they developed numerous capillary microaneurysms that ruptured at late gestation. Endothelial cells of the sprouting capillaries in the mutant mice appeared to be unable to attract PDGF-Rbeta-positive pericyte progenitor cells. Pericytes may contribute to the mechanical stability of the capillary wall. Comparisons made between PDGF null mouse phenotypes suggest a general role for PDGFs in the development of myofibroblasts.
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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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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                13 November 2018
                2018
                : 5
                : 317
                Affiliations
                [1] 1Section for Cardioimmunology, Department of Cardiovascular Medicine, University of Tuebingen , Tübingen, Germany
                [2] 2University Clinic for Cardiovascular Medicine, University of Tuebingen , Tübingen, Germany
                Author notes

                Edited by: Ana Kasirer-Friede, University of California, San Diego, United States

                Reviewed by: Wei Li, Marshall University, United States; Adrienn Angyal, University of Sheffield, United Kingdom

                *Correspondence: Harald F. Langer harald.langer@ 123456med.uni-tuebingen.de

                This article was submitted to Hematology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2018.00317
                6242949
                30483508
                89a46ec9-af98-403f-9bab-9d24f4495e8a
                Copyright © 2018 Eisinger, Patzelt and Langer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 March 2018
                : 23 October 2018
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 202, Pages: 15, Words: 12690
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: KFO 274
                Funded by: Volkswagen Foundation 10.13039/501100001663
                Award ID: Lichtenberg program
                Categories
                Medicine
                Review

                platelets,innate immunity,inflammation,infection,cytokines,leukocytes,complement,tissue remodeling

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