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      The Sweet-Side of Leukocytes: Galectins as Master Regulators of Neutrophil Function

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          Abstract

          Among responders to microbial invasion, neutrophils represent one of the earliest and perhaps most important factors that contribute to initial host defense. Effective neutrophil immunity requires their rapid mobilization to the site of infection, which requires efficient extravasation, activation, chemotaxis, phagocytosis, and eventual killing of potential microbial pathogens. Following pathogen elimination, neutrophils must be eliminated to prevent additional host injury and subsequent exacerbation of the inflammatory response. Galectins, expressed in nearly every tissue and regulated by unique sensitivity to oxidative and proteolytic inactivation, appear to influence nearly every aspect of neutrophil function. In this review, we will examine the impact of galectins on neutrophils, with a particular focus on the unique biochemical traits that allow galectin family members to spatially and temporally regulate neutrophil function.

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          Most cited references173

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          Cell death: critical control points.

          Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
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            Galectins as modulators of tumour progression.

            Galectins are a family of animal lectins with diverse biological activities. They function both extracellularly, by interacting with cell-surface and extracellular matrix glycoproteins and glycolipids, and intracellularly, by interacting with cytoplasmic and nuclear proteins to modulate signalling pathways. Current research indicates that galectins have important roles in cancer; they contribute to neoplastic transformation, tumour cell survival, angiogenesis and tumour metastasis. They can modulate the immune and inflammatory responses and might have a key role helping tumours to escape immune surveillance. How do the different members of the Galectin family contribute to these diverse aspects of tumour biology?
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              The role of neutrophils during intestinal inflammation.

              Polymorphonuclear leukocytes or neutrophils play a critical role in the maintenance of intestinal homeostasis. They have elegant defense mechanisms to eliminate microbes that have translocated across a single layer of mucosal epithelial cells that form a critical barrier between the gut lumen and the underlying tissue. During the inflammatory response, neutrophils also contribute to the recruitment of other immune cells and facilitate mucosal healing by releasing mediators necessary for the resolution of inflammation. Although the above responses are clearly beneficial, excessive recruitment and accumulation of activated neutrophils in the intestine under pathological conditions such as inflammatory bowel disease is associated with mucosal injury and debilitating disease symptoms. Thus, depending on the circumstances, neutrophils can be viewed as either good or bad. In this article, we summarize the beneficial and deleterious roles of neutrophils in the intestine during health and disease and provide an overview of what is known about neutrophil function in the gut.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                07 August 2019
                2019
                : 10
                : 1762
                Affiliations
                [1] 1Department of Laboratory Medicine and Pathology, Center for Transfusion Medicine and Cellular Therapies, Emory University School of Medicine , Atlanta, GA, United States
                [2] 2Department of Biochemistry, Brigham Young University , Provo, UT, United States
                [3] 3Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo , São Paulo, Brazil
                [4] 4Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Monica M. Burdick, Ohio University, United States

                Reviewed by: Sachiko Sato, Laval University, Canada; Petya Dimitrova, Institute of Microbiology (BAS), Bulgaria

                *Correspondence: Sean R. Stowell srstowe@ 123456emory.edu

                This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2019.01762
                6693361
                31440233
                71cd0ae2-a7c2-4b9d-8bb3-164e73b6f777
                Copyright © 2019 Robinson, Arthur, Evavold, Roback, Kamili, Stowell, Vallecillo-Zúniga, Van Ry, Dias-Baruffi, Cummings and Stowell.

                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
                : 07 February 2019
                : 11 July 2019
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 193, Pages: 17, Words: 13877
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Funded by: Burroughs Wellcome Fund 10.13039/100000861
                Categories
                Immunology
                Review

                Immunology
                neutrophil,galectin,glycoscience,inflammation,glycans
                Immunology
                neutrophil, galectin, glycoscience, inflammation, glycans

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