15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Phagocytosis of Apoptotic Cells in Resolution of Inflammation

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Efficient inflammation resolution is important not only for the termination of the inflammatory response but also for the restoration of tissue integrity. An integral process to resolution of inflammation is the phagocytosis of dying cells by macrophages, known as efferocytosis. This function is mediated by a complex and well-orchestrated network of interactions amongst specialized phagocytic receptors, bridging molecules, as well as “find-me” and “eat-me” signals. Efferocytosis serves not only as a waste disposal mechanism (clearance of the apoptotic cells) but also promotes a pro-resolving phenotype in efferocytic macrophages and thereby termination of inflammation. Alterations in cellular metabolism are critical for shaping the phenotype and function of efferocytic macrophages, thus, representing an important determinant of macrophage plasticity. Impaired efferocytosis can result in inflammation-associated pathologies or autoimmunity. The present mini review summarizes current knowledge regarding the mechanisms regulating macrophage efferocytosis during clearance of inflammation.

          Related collections

          Most cited references74

          • Record: found
          • Abstract: found
          • Article: not found

          Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.

          Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Resolution of inflammation: an integrated view

            Resolution of inflammation is a coordinated and active process aimed at restoration of tissue integrity and function. This review integrates the key molecular and cellular mechanisms of resolution. We describe how abrogation of chemokine signalling blocks continued neutrophil tissue infiltration and how apoptotic neutrophils attract monocytes and macrophages to induce their clearance. Uptake of apoptotic neutrophils by macrophages reprograms macrophages towards a resolving phenotype, a key event to restore tissue homeostasis. Finally, we highlight the therapeutic potential that derives from understanding the mechanisms of resolution.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Neutrophils as protagonists and targets in chronic inflammation

              Neutrophils are rapidly recruited to tissues in response to injury or infection, and they have mainly been studied in the context of acute inflammation. However, neutrophils can also be important contributors to chronic tissue inflammation. This Review discusses neutrophil function in the context of chronic inflammation and considers the potential of targeting these cells in chronic diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                31 March 2020
                2020
                : 11
                : 553
                Affiliations
                [1] 1Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden , Dresden, Germany
                [2] 2Hull York Medical School, York Biomedical Research Institute, University of York , York, United Kingdom
                [3] 3Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, Department of Basic and Translational Sciences, University of Pennsylvania , Philadelphia, PA, United States
                [4] 4Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh , Edinburgh, United Kingdom
                Author notes

                Edited by: Esther M. Lafuente, Complutense University of Madrid, Spain

                Reviewed by: Amiram Ariel, University of Haifa, Israel; Jeffrey Louis Curtis, University of Michigan Medical School, United States

                *Correspondence: Ioannis Kourtzelis, ioannis.kourtzelis@ 123456york.ac.uk

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

                Article
                10.3389/fimmu.2020.00553
                7137555
                32296442
                1c30aacc-f42f-47e1-bf2f-9c1c402b11cf
                Copyright © 2020 Kourtzelis, Hajishengallis and Chavakis.

                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
                : 12 January 2020
                : 11 March 2020
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 115, Pages: 8, Words: 0
                Categories
                Immunology
                Mini Review

                Immunology
                phagocytosis,efferocytosis,del-1,immunometabolism,inflammation resolution,integrins
                Immunology
                phagocytosis, efferocytosis, del-1, immunometabolism, inflammation resolution, integrins

                Comments

                Comment on this article