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      Neutrophil-derived chemokines on the road to immunity

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          Highlights

          • Neutrophils represent a cellular source of chemokines.

          • Neutrophils recruit and activate, via chemokines, discrete leukocyte populations.

          • Neutrophils, in virtue of their capacity to recruit innate and adaptive immunity cells via chemokines, potentially orchestrate sophisticated immune responses.

          • Neutrophil-derived chemokines contribute to the pathogenesis of infectious and non-infectious diseases.

          Abstract

          During recent years, it has become clear that polymorphonuclear neutrophils are remarkably versatile cells, whose functions go far beyond phagocytosis and killing. In fact, besides being involved in primary defense against infections–mainly through phagocytosis, generation of toxic molecules, release of toxic enzymes and formation of extracellular traps–neutrophils have been shown to play a role in finely regulating the development and the evolution of inflammatory and immune responses. These latter neutrophil-mediated functions occur by a variety of mechanisms, including the production of newly manufactured cytokines.

          Herein, we provide a general overview of the chemotactic cytokines/chemokines that neutrophils can potentially produce, either under inflammatory/immune reactions or during their activation in more prolonged processes, such as in tumors. We highlight recent observations generated from studying human or rodent neutrophils in vitro and in vivo models. We also discuss the biological significance of neutrophil-derived chemokines in the context of infectious, neoplastic and immune-mediated diseases. The picture that is emerging is that, given their capacity to produce and release chemokines, neutrophils exert essential functions in recruiting, activating and modulating the activities of different leukocyte populations.

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          Most cited references80

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          Neutrophil-Derived Cytokines: Facts Beyond Expression

          Polymorphonuclear neutrophils, besides their involvement in primary defense against infections – mainly through phagocytosis, generation of toxic molecules, release of enzymes, and formation of extracellular traps – are also becoming increasingly important for their contribution to the fine regulation in development of inflammatory and immune responses. These latter functions of neutrophils occur, in part, via their de novo production and release of a large variety of cytokines, including chemotactic cytokines (chemokines). Accordingly, the improvement in technologies for molecular and functional cell analysis, along with concomitant advances in cell purification techniques, have allowed the identification of a continuously growing list of neutrophil-derived cytokines, as well as the characterization of their biological implications in vitro and/or in vivo. This short review summarizes crucial concepts regarding the modalities of expression, release, and regulation of neutrophil-derived cytokines. It also highlights examples illustrating the potential implications of neutrophil-derived cytokines according to recent observations made in humans and/or in experimental animal models.
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            Chemokines in cancer.

            Chemokines are chemotactic cytokines that control the migration of cells between tissues and the positioning and interactions of cells within tissue. The chemokine superfamily consists of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven-transmembrane spanning signaling receptors. Chemokines mediate the host response to cancer by directing the trafficking of leukocytes into the tumor microenvironment. This migratory response is complex and consists of diverse leukocyte subsets with both antitumor and protumor activities. Although chemokines were initially appreciated as important mediators of immune cell migration, we now know that they also play important roles in the biology of nonimmune cells important for tumor growth and progression. Chemokines can directly modulate the growth of tumors by inducing the proliferation of cancer cells and preventing their apoptosis. They also direct tumor cell movement required for metastasis. Chemokines can also indirectly modulate tumor growth through their effects on tumor stromal cells and by inducing the release of growth and angiogenic factors from cells in the tumor microenvironment. In this Masters of Immunology primer, we focus on recent advances in understanding the complex nature of the chemokine system in tumor biology with a focus on how the chemokine system could be used to augment cancer immunotherapeutic strategies to elicit a more robust and long-lasting host antitumor immune response.
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              Neutrophils cascading their way to inflammation.

              Neutrophils are pivotal effector cells of innate immunity. Their recruitment into peripheral tissues is indispensable for host defense. Given their destructive potential, neutrophil entry into tissue must be tightly regulated in vivo to avoid damage to the host. An array of chemically diverse chemoattractants is active on neutrophils and participates in recruitment. Neutrophil chemoattractants were thought redundant in the control of neutrophil recruitment into peripheral tissue, based on their often indistinguishable effects on neutrophils in vitro and their frequently overlapping patterns of expression at inflammatory sites in vivo. Recent data, however, suggest that neutrophil chemoattractants have unique functions in the recruitment of neutrophils into inflammatory sites in vivo, dictated by their distinct patterns of temporal and spatial expression. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Semin Immunol
                Semin. Immunol
                Seminars in Immunology
                Published by Elsevier Ltd.
                1044-5323
                1096-3618
                14 April 2016
                April 2016
                14 April 2016
                : 28
                : 2
                : 119-128
                Affiliations
                [a ]Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy
                [b ]Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy
                Author notes
                [* ]Corresponding authors at: Department of Medicine, Hematology and Bone Marrow Transplant Unit, Piazzale L.A. Scuro and, Section of General Pathology, Strada Le Grazie 8, 37134 Verona, Italy. cristina.tecchio@ 123456univr.it marco.cassatella@ 123456univr.it
                [1]

                Department of Medicine, Section of General Pathology, Strada Le Grazie 8, 37134 Verona, Italy.

                Article
                S1044-5323(16)30017-3
                10.1016/j.smim.2016.04.003
                7129466
                27151246
                61dd15c1-f1c9-4718-9a12-d76aef4978b2
                © 2016 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 23 March 2016
                : 4 April 2016
                : 5 April 2016
                Categories
                Article

                Immunology
                neutrophils,chemokines,innate immunity,adaptive immunity,infections,tumors,immune-mediated diseases

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