DOCSLIB.ORG

Efferocytosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Efferocytosis Encyclopedia of Cancer DOI 10.1007/978-3-642-27841-9_7215-1 # Springer-Verlag Berlin Heidelberg 2015 Efferocytosis Nikko Brix*, Anna Tiefenthaller and Kirsten Lauber Clinic for Radiotherapy and Radiation Oncology, LMU Munich, Munich, Germany Keywords Apoptosis; Necrosis; Phagocytes; Macrophages; Dendritic cells; Immune response; Inflammation; Immune tolerance; Autoimmunity; Cancer; “Find-me” signals; “Eat-me” signals; “Don’t-eat-me” signals Definition The term efferocytosis (from effere, Latin for “to take away”, “to carry to the grave”, “to bury”) has been defined as the process of apoptotic cell removal, which involves phagocyte recruitment, dying cell recognition, and engulfment. Characteristics The Efferocytic Process Apoptotic Cell Death In higher multicellular organisms, the removal of dying cells is a common event: It is estimated that one million cells undergo apoptosis per second in a human adult, and fundamental biological processes, such as embryogenesis, the resolution of inflammation, or homeostatic cell turnover involve apoptosis and subsequent clearance of dying cells. This is performed either by neighboring cells (when they are endowed with “amateur” phagocyte capacity) or by professional phagocytes, such as macrophages and immature dendritic cells (DCs), respectively. Macrophages and DCs serve as “undertakers” of dying cells with different tasks. Whereas macrophages can powerfully engulf and degrade huge amounts of dying cell material, DCs act as sentinels, which capture antigen and (cross-)present it to T cells, thus sculpting adaptive immune responses. The entire process of apoptosis is finely controlled, swift, and innoxious for the surrounding tissue. These characteristics starkly distinguish it from the events being observed during necrosis, which is considered to be a nonphysiological form of cell death where plasma membrane rupture and the uncontrolled release of cytosolic danger signals occur. Importantly, apoptosis is an immunogenically silent event. It is morphologically characterized by cell shrinking, chromatin condensation, nuclear fragmentation, and plasma membrane blebbing. On the molecular level, a set of proteases termed caspases commonly initiate and execute this form of programmed cell death. Besides, caspase-independent forms of apoptosis have been reported. The integrity of organelles and the plasma membrane is preserved until late stages of apoptosis. Thus, the liberation of pro-inflammatory intracellular molecules, including heat shock proteins, high mobility group box 1 protein (HMGB1), S100 proteins, and uric acid, which may damage neighboring cells and induce inflammation, is prevented. *Email: [email protected] Page 1 of 7 Encyclopedia of Cancer DOI 10.1007/978-3-642-27841-9_7215-1 # Springer-Verlag Berlin Heidelberg 2015 Phagocyte Recruitment by Apoptotic Cells In order to “orchestrate” their own burial, apoptotic cells send out soluble chemotactic factors to trigger monocyte/macrophage recruitment, which is a premise for efficient efferocytosis. These “find-me” signals comprise biomolecules of very different classes, such as nucleotides (mainly ATP and UTP), phospho- lipids (e.g. lysophosphatidylcholine and sphingosine-1-phosphate), and proteins (for instance, the ectodomain of the IL-6 receptor and soluble fractalkine), which are recognized by the corresponding phagocyte receptors. Recognition of Apoptotic Cells by Phagocytes Upon attraction to the apoptotic site, phagocytes must precisely distinguish between healthy and dying cells. This substep of the efferocytic cascade is guided by the exposure of “eat-me” signals on the apoptotic cell surface. Translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the best-known and probably most important example. This phospholipid is recognized by bona fide PS receptors on the phagocytes (e.g. brain angiogenesis inhibitor 1 (BAI-1), T cell immunoglobulin mucin domain (TIM) family members 1, 3, and 4, and the stabilins 1 and 2) or indirectly via soluble bridging proteins, which bind to both PS and their respective phagocytic cell surface receptors. Examples of bridging proteins secreted by phagocytes are milk fat globule EGF factor 8 (MFG-E8) and developmental endothelial locus 1 (Del-1). Moreover, bridging proteins derived from apoptotic cells, such as annexin A1, or from interstitial body fluids (b2-glycoprotein, growth arrest specific gene 6 (GAS6), and protein S) have been described. Furthermore, additional “eat-me” signals apart from PS exist. Examples are the surface exposure of ICAM-3 on apoptotic cells being recognized by CD14 and altered sugars, which are detected by lectins on the phagocyte. Besides, the inactivation and/or the lack of “don’t-eat-me” signals (e.g. CD47 and CD46) contribute to efficient dying cell engulfment. These proteins are expressed on healthy cells and thus protect them from being accidentally ingested by phagocytes. Taken together, a plethora of different signals mediate the engulfment of apoptotic cells, and it is currently being unraveled which receptor- ligand axis dominates in which tissue or organ. Apoptotic Cell Engulfment The signaling mechanisms that are initiated upon ligation of phagocytic “eat-me” signal receptors are far from being fully understood. Yet, it is known that the ingestion of apoptotic cells requires massive modifications in the phagocyte’s actin cytoskeleton. These are regulated by small GTPases of the RHO family, such as RHOA, RAC, and CDC42. RHOA activation has been described to inhibit apoptotic cell engulfment via binding and thereby activating its downstream effector Rho-associated coiled-coil containing protein kinase (ROCK). ROCK activation may in turn alter the phosphorylation status of myosin light chain and thus the phagocytic actin cytoskeleton structure and contractility. Inversely, RHOA inhibition was shown to promote dying cell engulfment. In contrast to RHOA, RAC activation positively affects apoptotic cell engulfment. For instance, the PS receptor BAI-1 is known to activate RAC by recruiting the adaptor protein engulfment and cell motility 1 (ELMO1) and its binding partner dedicator of cytokinesis 180 (DOCK180). The Post-Phagocytic Immune Response Apoptotic cell death itself is not only immunogenically silent, it also shapes the post-phagocytic immune response. Unlike the uptake of necrotic cell material by macrophages, apoptotic cell engulfment induces the secretion of anti-inflammatory cytokines including interleukin-10 (IL-10), transforming growth factor b (TGF-b), and prostaglandin E2 (PGE2). The removal of apoptotic cell material by DCs that have been educated in this milieu leads to tolerogenic (cross-)presentation of antigens in the draining lymph nodes. Page 2 of 7 Encyclopedia of Cancer DOI 10.1007/978-3-642-27841-9_7215-1 # Springer-Verlag Berlin Heidelberg 2015 Among the “tolerate-me” signals, which are involved in the immunomodulatory processes being initiated upon apoptotic cell clearance, exposure of PS is of crucial importance. However, since PS exposure is also observed during necrosis after plasma membrane rupture, it is evident that several other biomolecules might contribute to sculpting the immunological outcome of dying cell phagocytosis. Moreover, the cause of apoptotic cell death, the predominating dying cell type, and the quantity of apoptotic cells naturally modify the post-phagocytic immune response. The latter point is of particular importance: Although efferocytosis is performed rapidly under physiological conditions, excessive apoptotic cell death and/or inefficient clearance may overwhelm the phagocytic capacity: For instance, accumulating, uncleared apoptotic cells can be observed in the context of autoimmune diseases or after tumor radio(chemo)therapy as discussed below. As a result, these apoptotic cells may transit into secondary necrosis culminating in plasma membrane rupture and liberation of pro-inflammatory intracellular components. Considering their disparate origin, the soluble mediators released from primary and secondary necrotic cells encode for different immunological outcomes but commonly induce pro-inflammatory processes, which may atten- uate the anti-inflammatory milieu at a formerly apoptotic site. Diseases Caused by Malfunctioning Efferocytosis The fact that apoptotic cells are rarely seen in homeostatic tissues testifies the efficiency of dying cell removal by professional and “amateur” phagocytes. In case of malfunctioning dying cell clearance, insufficient immunological quiescence causes recruitment of inflammatory cells into the tissue. Accumu- lation of this cell debris might initiate immunological reactions against self-antigens resulting in different types of chronic inflammatory diseases. Rheumatic Diseases The term “rheumatism” summarizes a wide range of autoimmune diseases affecting different organs. Their common pathogenesis is associated to autoimmune mechanisms – immune reactions against the body’s own tissues. From an immunological point of view, defective efferocytosis after tissue destruction leads to accu- mulation of cell corpses, which progress into secondary necrosis and release their intracellular contents (e.g., DNA, nucleosomes, and histones) upon cell membrane rupture. The immune system generates antibodies against these intracellular antigens, which in complex with their cognate antigens can stimulate an exacerbation of the inflammatory cascade. The immune reaction against own tissue structures and intracellular components results in general symptoms such as fever,
Load more

Recommended publications
  • Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 8-15-2014 12:00 AM Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies Yohan Kim The University of Western Ontario Supervisor Dr. Bryan Heit The University of Western Ontario Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Yohan Kim 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cell Biology Commons, Immunity Commons, and the Other Immunology and Infectious Disease Commons Recommended Citation Kim, Yohan, "Characterization of Efferosome Maturation and the Processing of Apoptotic Bodies" (2014). Electronic Thesis and Dissertation Repository. 2268. https://ir.lib.uwo.ca/etd/2268 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. CHARACTERIZATION OF EFFEROSOME MATURATION AND THE PROCESSING OF APOPTOTIC BODIES (Thesis format: Monologue) by Yohan Kim Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Yohan Kim 2014 Abstract Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens.
    [Show full text]
  • Elucidating the Signalling Pathway of Mer Tyrosine Kinase Receptor in Efferocytosis
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 8-19-2014 12:00 AM Elucidating the Signalling Pathway of Mer Tyrosine Kinase Receptor in Efferocytosis Ekenedelichukwu Azu The University of Western Ontario Supervisor Dr. Bryan Heit The University of Western Ontario Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Ekenedelichukwu Azu 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cell Biology Commons, Immunity Commons, Molecular Biology Commons, and the Other Immunology and Infectious Disease Commons Recommended Citation Azu, Ekenedelichukwu, "Elucidating the Signalling Pathway of Mer Tyrosine Kinase Receptor in Efferocytosis" (2014). Electronic Thesis and Dissertation Repository. 2260. https://ir.lib.uwo.ca/etd/2260 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. ELUCIDATING THE SIGNALLING PATHWAY OF MER TYROSINE KINASE RECEPTOR IN EFFEROCYTOSIS Thesis format: Monograph by Ekenedelichukwu Azu Graduate Program in Microbiology and Immunology A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Ekenedelichukwu Azu 2014 Abstract Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown.
    [Show full text]
  • Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators On
    antioxidants Review Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation 1, 1,2, 2, Gyeoung Jin Kang y, Eun Ji Kim y and Chang Hoon Lee * 1 Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] (G.J.K.); [email protected] (E.J.K.) 2 College of Pharmacy, Dongguk University, Seoul 04620, Korea * Correspondence: [email protected]; Tel.: +82-31-961-5213 Equally contributed. y Received: 11 November 2020; Accepted: 9 December 2020; Published: 10 December 2020 Abstract: Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation. Keywords: cardiac fibrosis; NRF2; lipoxins; resolvins; maresins; neuroprotectins 1. Introduction Cardiovascular disease is the leading cause of death worldwide [1]. Cardiac fibrosis is a major factor leading to the progression of myocardial infarction and heart failure [2]. Cardiac fibrosis is characterized by the net accumulation of extracellular matrix proteins in the cardiac stroma and ultimately impairs cardiac function [3]. Therefore, interest in substances with cardioprotective activity continues.
    [Show full text]
  • Emerging Functions of ICAM-1 in Macrophage Efferocytosis and Wound Healing
    https://www.scientificarchives.com/journal/journal-of-cellular-immunology Journal of Cellular Immunology Commentary Emerging Functions of ICAM-1 in Macrophage Efferocytosis and Wound Healing Prarthana J. Dalal, Ronen Sumagin* Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA *Correspondence should be addressed to Ronen Sumagin; [email protected] Received date: July 21, 2020 , Accepted date: August 17, 2020 Copyright: © 2020 Dalal PJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: ICAM-1, Efferocytosis, Wound healing, ICAM-1 and Efferocytosis Inflammation, Migration, Adhesion Efferocytosis is a specialized process for the clearance of Introduction apoptotic cells (ACs) by tissue macrophages. It is essential for maintaining tissue homeostasis and when impaired can ICAM-1 is a transmembrane, cell surface glycoprotein lead to non-resolving pathologic inflammation and tissue expressed by a variety of cells, but has been best-studied in injury. Effective efferocytosis involves recognition of AC- vascular endothelium. Structurally, ICAM-1 is composed associated ligands by macrophages via specialized surface of five extracellular IgG- like domains to help facilitate receptors, reorganization of the macrophage cytoskeleton cell-cell interactions and has a short cytoplasmic tail during AC engulfment, as well as phagolysosome fusion anchored to the cytoskeleton to facilitate intracellular within the macrophages to degrade the internalized ACs. signal transduction. ICAM-1 expressed by endothelial cells binds β2-integrins, CD11b/CD18 (Mac1), and CD11a/CD18 Macrophages express a number of efferocytotic receptors (LFA1) to mediate the adhesion of circulating leukocytes to including the TAM family tyrosine kinases (Tyro3, Axl, the vessel wall and to facilitate transendothelial migration and Mer) [12].
    [Show full text]
  • Endocytic Deficiency Induced by ITSN-1S Knockdown Alters the Smad2/3-Erk1/2 Signaling Balance Downstream of Alk5
    ß 2015. Published by The Company of Biologists Ltd | Journal of Cell Science (2015) 128, 1528–1541 doi:10.1242/jcs.163030 RESEARCH ARTICLE Endocytic deficiency induced by ITSN-1s knockdown alters the Smad2/3-Erk1/2 signaling balance downstream of Alk5 Cristina Bardita1, Dan N. Predescu1,2, Fei Sha1, Monal Patel1, Ganesh Balaji3 and Sanda A. Predescu1,2,* ABSTRACT leading to pulmonary edema, evidence suggests that apoptosis plays a beneficial role during ALI resolution owing to the pro- Recently, we demonstrated in cultured endothelial cells and in vivo regenerative role of clearance of apoptotic cells (Predescu et al., that deficiency of an isoform of intersectin-1, ITSN-1s, impairs 2013; Schmidt and Tuder, 2010). This effect is mediated through caveolae and clathrin-mediated endocytosis and functionally the production of growth factors including TGFb by macrophages upregulates compensatory pathways and their morphological engulfing apoptotic cells, or perhaps by other vascular cells carriers (i.e. enlarged endocytic structures, membranous rings or (Bardita et al., 2013; Henson and Tuder, 2008). TGFb, owing to tubules) that are normally underrepresented. We now show that its anti-inflammatory properties confines the extent of septal these endocytic structures internalize the broadly expressed injury and speeds recovery in ALI (D’Alessio et al., 2009). transforming growth factor b receptor I (TGFb-RI or TGFBR1), We have recently shown that in vivo deficiency of ITSN-1s, an also known as Alk5, leading to its ubiquitylation and degradation. isoform of ITSN-1 that is highly prevalent in lung endothelium and Moreover, the apoptotic or activated vascular cells of the ITSN-1s- deficiency of which is relevant to the pathology of ALI/ARDS knockdown mice release Alk5-bearing microparticles to the (Bardita et al., 2013; Predescu et al., 2013), induces extensive lung systemic circulation.
    [Show full text]
  • Type-1 IFN Primed Monocytes in Pathogenesis of Idiopathic Pulmonary Fibrosis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.16.908749; this version posted January 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis Emily Fraser1**, Laura Denney1**, Karl Blirando1, Chaitanya Vuppusetty1, Agne Antanaviciute1, Yuejuan Zheng1,6, Emmanouela Repapi3, Valentina Iotchkova3, Stephen Taylor3, Neil Ashley4, Victoria St Noble5, Rachel Benamore5, Rachel Hoyles5, Colin Clelland5, Joseph M D Rastrick7, Clare S Hardman1, Nasullah K Alham8, Rachel E Rigby1, Jan Rehwinkel1 and Ling-Pei Ho1,2* Affiliations: 1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford. 2Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation Trust, Oxford. 3Department of Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford. 4 Single Cell Genomics Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK 5Department of Thoracic Imaging, Oxford University Hospitals NHS Foundation Trust, Oxford. 6Department of Immunology and Microbiology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China 7Immunology Therapeutic Area, UCB Pharma, Slough, UK. 8Nuffield Department of Surgical Sciences and Oxford NIHR Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford *To whom correspondence should be addressed: [email protected] **Joint first authors The authors have declared that no conflict of interest exists. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.01.16.908749; this version posted January 17, 2020.
    [Show full text]
  • Defective Efferocytosis by Alveolar Macrophages in IPF Patients
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Respiratory Medicine (2012) 106, 1800e1803 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/rmed SHORT COMMUNICATION Defective efferocytosis by alveolar macrophages in IPF patients Konosuke Morimoto a,*, William J. Janssen b, Mayumi Terada a a Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan b Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, Denver, CO, USA Received 13 July 2012; accepted 27 August 2012 Available online 19 September 2012 KEYWORDS Summary Idiopathic pulmonary Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial fibrosis; pneumonia. The pathogenicity of IPF has been widely investigated but still remains to be clar- Efferocytosis; ified. Efferocytosis, the specialized recognition and ingestion of apoptotic cells by phagocytes, BAL; is essential for the resolution of inflammation in the lungs and repair of injured tissues. Idiopathic interstitial Impaired efferocytosis contributes to the pathogenesis of chronic lung diseases such as emphy- pneumonia sema and cystic fibrosis. We hypothesized that efferocytosis would also be reduced in alveolar macrophages isolated from subjects with IPF. Methods: Efferocytosis, was evaluated using Wright-Giemsa stained cell preparations isolated from the bronchoalveolar lavage (BAL) fluid of patients with IPF (n Z 5), nonspecific intersti- tial pneumonitis (n Z 6), cryptogenic organizing pneumonia (n Z 4) and eosinophilic pneu- monia (EP) (n Z 5). Results: Uningested apoptotic cells were significantly higher in BAL fluid from patients with IPF compared to other forms of interstitial lung disease.
    [Show full text]
  • Phosphatidylserine Hide-And-Seek COMMENTARY
    COMMENTARY Phosphatidylserine hide-and-seek COMMENTARY Suzanne Corya,b,1 Every day, billions of new cells are produced in our sites within a cytoplasmic loop; once apoptosis is acti- bodies, and an equivalent number must die. Normally vated, cleavage of these sites irreversibly inactivates this occurs by apoptosis (1), during which the chroma- their flippase function (Fig. 1B). However, while it is tin compacts against the nuclear envelope, followed an obligatory step, loss of flippase activity is not suffi- rapidly by nuclear fragmentation and budding into cient to rapidly expose PtdSer due, in part, to the un- multiple membrane-bound apoptotic bodies. This favorable kinetics of a phospholipid with a polar head “dance of death” results from the activation of certain group moving through the hydrophobic lipid layer. Thus, proteases known as caspases, culminating in activa- efferocytosis cannot proceed unless the target cells tion of effector caspases-3 and -7, which target hun- also activate a scramblase, which can translocate phos- dreds of vital cellular proteins. Importantly, because pholipids bidirectionally between the inner and outer there is no cell membrane rupture, apoptotic cell leaflet of the plasma membrane. death provokes no inflammatory response, in contrast Using heroic expression cloning, Nagata and co- to cell death by necrosis, necroptosis, or pyroptosis. workers (6, 7) previously identified two such scram- However, in our bodies, as in our communities, proper blases, XKR8 and TMEM16F, each of which is ubiq- disposal of detritus is vital for our health. Thus, the ap- uitously expressed and belongs to an extended protein optotic corpses are recognized and rapidly removed by family.
    [Show full text]
  • Apoptotic Cell Clearance Basic Biology and Therapeutic Potential
    Edinburgh Research Explorer Apoptotic cell clearance Citation for published version: Poon, IKH, Lucas, CD, Rossi, AG & Ravichandran, KS 2014, 'Apoptotic cell clearance: basic biology and therapeutic potential', Nature Reviews Immunology, vol. 14, no. 3, pp. 166-180. https://doi.org/10.1038/nri3607 Digital Object Identifier (DOI): 10.1038/nri3607 Link: Link to publication record in Edinburgh Research Explorer Document Version: Peer reviewed version Published In: Nature Reviews Immunology Publisher Rights Statement: Published in final edited form as: Nat Rev Immunol. Mar 2014; 14(3): 166–180. General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 27. Sep. 2021 NIH Public Access Author Manuscript Nat Rev Immunol. Author manuscript; available in PMC 2014 September 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nat Rev Immunol. 2014 March ; 14(3): 166–180. doi:10.1038/nri3607. Apoptotic cell clearance: basic biology and therapeutic potential Ivan K. H. Poon1,2,*, Christopher D. Lucas3,*, Adriano G. Rossi3, and Kodi S.
    [Show full text]
  • Role of Specialized Pro-Resolving Lipid Mediators in Pulmonary
    Yang et al. Respir Res (2021) 22:204 https://doi.org/10.1186/s12931-021-01792-y REVIEW Open Access Role of specialized pro-resolving lipid mediators in pulmonary infammation diseases: mechanisms and development Ailin Yang, Yanjun Wu, Ganggang Yu* and Haoyan Wang* Abstract Infammation is an essential mechanism of various diseases. The development and resolution of infammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in infammation. SPMs are involved in the pathophysiology of diferent diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the infammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of infammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases. Keywords: Infammation resolution, Lung diseases, Lung infammation, Pro-resolving lipid mediators, Mechanism Introduction have shown that chronic, persistent infammation might Infammation is a major defense mechanism of the be the cause of cancer, neurodegenerative diseases [5] human body. If the body is subjected to an injury, infec- (e.g., Alzheimer’s disease, Parkinson disease) and even tion, or other similar stimuli, the innate immune system certain types of mental illness [6]. becomes activated within seconds-to-minutes. Innate Acute infammation is induced by the innate immune immunity is useful in promoting infammation and can system, which has an essential protective role, prevents aid in determining the level of pathogenic invasion or some infections, and promotes healing in injured tis- stimuli.
    [Show full text]
  • Specialized Pro-Resolving Mediators
    Specialized Pro-Resolving Mediators Specialized pro-resolving mediators (SPMs) are an important group of signaling molecules derived from arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid that is liberated during the inflammatory process. Studies have shown that resolvins, lipoxins, maresins, and protectins evoke responses that help to resolve an inflammatory episode. Cayman has synthesized an array of these key lipid mediators to aid in a better understanding of this process. Sin SPMs RESOLVE INFLAMMATORY Post inury RESPONSE AFTER INJURY/INFECTION + Lipoxins + Protectins Cytoines SPMs + Maresins + E-, D-, and T-Series Resolvins Chemoines Lipids Request the SPM Pathway Wall Poster at Blood vessel www.caymanchem.com/Literature Pro-Resolving Compounds Resolvins Lipoxins, Maresins, and Protectins Item No. Product Name Item No. Product Name ® ® 10012554 Resolvin D1 (MaxSpec Standard Also Available) 90410 Lipoxin A4 (MaxSpec Standard Also Available) ® 13060 17(R)-Resolvin D1 10007737 Lipoxin A4-d5 (MaxSpec Standard Also Available) 10007279 Resolvin D2 90420 Lipoxin B4 11184 Resolvin D2-d5 10878 Maresin 1 13834 Resolvin D3 16369 Maresin 2 19512 Resolvin D3-d5 17007 MCTR1 9002686 Resolvin D3 methyl ester 17008 MCTR2 13835 Resolvin D4 19067 MCTR3 10007280 Resolvin D5 19064 PCTR1 10007848 Resolvin E1 19065 PCTR2 10009854 Resolvin E1-d4 19066 PCTR3 Common SPMs listed, more compounds including methyl ester and deuterated forms available online MaxSpec® Standards MaxSpec® Quality Guarantee MAXIMIZE RESULTS Verified concentration LC-MS identity tested Cayman's line of ready-to-use, quantitative standards HPLC purity tested designed to simplify mass spectrometry workflows. Ongoing stability testing Now Available! Resolvin D1, Lipoxin A4, Lipoxin A4-d5, Maresin 1-d5 , and 14(S)-HDHA 2020 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Sensitive, Accurate Quantification of Lipoxin B 100 4 80 0 Lipoxin B4 ELISA Kit - Item No.
    [Show full text]
  • Apoptosis and Clearance of Apoptotic Cells
    IY36CH19_Nagata ARI 23 March 2018 8:38 Annual Review of Immunology Apoptosis and Clearance of Apoptotic Cells Shigekazu Nagata Laboratory of Biochemistry and Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Osaka 565–0871, Japan; email: [email protected] Annu. Rev. Immunol. 2018. 36:489–517 Keywords First published as a Review in Advance on apoptosis, efferocytosis, macrophages, phosphatidylserine, flippase, February 5, 2018 scramblase, caspase, TIM4, TAM receptors The Annual Review of Immunology is online at immunol.annualreviews.org Abstract https://doi.org/10.1146/annurev-immunol- The human body generates 10–100 billion cells every day, and the same 042617-053010 number of cells die to maintain homeostasis in our body. Cells infected by Annu. Rev. Immunol. 2018.36:489-517. Downloaded from www.annualreviews.org Access provided by Universidad de Guadalajara on 04/05/19. For personal use only. Copyright c 2018 by Annual Reviews. bacteria or viruses also die. The cell death that occurs under physiological All rights reserved conditions mainly proceeds by apoptosis, which is a noninflammatory, or silent, process, while pathogen infection induces necroptosis or pyropto- sis, which activates the immune system and causes inflammation. Dead cells ANNUAL generated by apoptosis are quickly engulfed by macrophages for degrada- REVIEWS Further Click here to view this article's tion. Caspases are a large family of cysteine proteases that act in cascades. A online features: cascade that leads to caspase 3 activation mediates apoptosis and is respon- • Download figures as PPT slides • Navigate linked references sible for killing cells, recruiting macrophages, and presenting an “eat me” • Download citations • Explore related articles signal(s).
    [Show full text]