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Apoptosis

, Volume 24, Issue 3–4, pp 208–220 | Cite as

Methods for monitoring the progression of cell death, cell disassembly and cell clearance

  • Lanzhou Jiang
  • Ivan K. H. PoonEmail author
Review
  • 538 Downloads

Abstract

Cell death through apoptosis, necrosis, necroptosis and pyroptosis, as well as the clearance of dead cells are crucial biological processes in the human body. Likewise, disassembly of dying cells during apoptosis to generate cell fragments known as apoptotic bodies may also play important roles in regulating cell clearance and intercellular communication. Recent advances in the field have led to the development of new experimental systems to identify cells at different stages of cell death, measure the levels of apoptotic cell disassembly, and monitor the cell clearance process using a range of in vitro, ex vivo and in vivo models. In this article, we will provide a comprehensive review of the methods for monitoring the progression of cell death, cell disassembly and cell clearance.

Keywords

Apoptosis Necrosis Pyroptosis Necroptosis Apoptotic cell disassembly Apoptotic bodies Efferocytosis Phagocytosis Cell clearance 

Notes

Funding

This study was funded by National Health and Medical Research Council (Grant Nos. GNT1125033, GNT1140187) and Australian Research Council (Grant No. DP170103790).

Supplementary material

10495_2018_1511_MOESM1_ESM.jpg (322 kb)
Supplementary material 1 (JPG 322 KB)

References

  1. 1.
    Atkin-Smith GK, Poon IKH (2016) Disassembly of the dying: mechanisms and functions. Trends Cell Biol.  https://doi.org/10.1016/j.tcb.2016.08.011 Google Scholar
  2. 2.
    Poon IKH, Lucas CD, Rossi AG, Ravichandran KS (2014) Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 14:166–180.  https://doi.org/10.1038/nri3607 Google Scholar
  3. 3.
    Agostini M, Tucci P, Melino G (2011) Cell death pathology: perspective for human diseases. Biochem Biophys Res Commun 414:451–455.  https://doi.org/10.1016/j.bbrc.2011.09.081 Google Scholar
  4. 4.
    Arandjelovic S, Ravichandran KS (2008) Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 44:280–285.  https://doi.org/10.1038/ni.3253 Google Scholar
  5. 5.
    Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306.  https://doi.org/10.1016/S0074-7696(08)62312-8 Google Scholar
  6. 6.
    Atkin-Smith GK, Tixeira R, Paone S et al (2015) A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat Commun 6:7439.  https://doi.org/10.1038/ncomms8439 Google Scholar
  7. 7.
    Moss DK, Betin VM, Malesinski SD, Lane JD (2006) A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation. J Cell Sci 119:2362–2374.  https://doi.org/10.1242/jcs.02959 Google Scholar
  8. 8.
    Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99–104.  https://doi.org/10.1038/sj.cdd.4400476 Google Scholar
  9. 9.
    Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501.  https://doi.org/10.1016/S0092-8674(00)81590-1 Google Scholar
  10. 10.
    Liu X, Zou H, Slaughter C, Wang X (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89:175–184.  https://doi.org/10.1016/S0092-8674(00)80197-X Google Scholar
  11. 11.
    Fink SL, Cookson BT (2005) Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun 73:1907–1916.  https://doi.org/10.1128/IAI.73.4.1907-1916.2005 Google Scholar
  12. 12.
    Galluzzi L, Kroemer G (2008) Necroptosis: a specialized pathway of programmed necrosis. Cell 135:1161–1163.  https://doi.org/10.1016/j.cell.2008.12.004 Google Scholar
  13. 13.
    Galluzzi L, Vitale I, Aaronson SA et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541.  https://doi.org/10.1038/s41418-017-0012-4 Google Scholar
  14. 14.
    Pasparakis M, Vandenabeele P (2015) Necroptosis and its role in inflammation. Nature 517:311–320.  https://doi.org/10.1038/nature14191 Google Scholar
  15. 15.
    Moriwaki K, Chan FKM (2016) Necroptosis-independent signaling by the RIP kinases in inflammation. Cell Mol Life Sci 73:2325–2334.  https://doi.org/10.1007/s00018-016-2203-4 Google Scholar
  16. 16.
    Aaes TL, Kaczmarek A, Delvaeye T et al (2016) Vaccination with necroptotic cancer cells induces efficient anti-tumor immunity. Cell Rep 15:274–287.  https://doi.org/10.1016/j.celrep.2016.03.037 Google Scholar
  17. 17.
    Yatim N, Jusforgues-Saklani H, Orozco S, et al (2015) RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells. Science.  https://doi.org/10.1126/science.aad0395 Google Scholar
  18. 18.
    Zhang Y, Chen X, Gueydan C, Han J (2017) Plasma membrane changes during programmed cell deaths. Cell Res 28(1):1–13.  https://doi.org/10.1038/cr.2017.133 Google Scholar
  19. 19.
    Shi J, Gao W, Shao F (2017) Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 42:245–254.  https://doi.org/10.1016/j.tibs.2016.10.004 Google Scholar
  20. 20.
    Bouchier-Hayes L, Munoz-Pinedo C, Connell S, Green DR (2008) Measuring apoptosis at the single cell level. Methods 44:222–228.  https://doi.org/10.1016/j.ymeth.2007.11.007
  21. 21.
    Vanden Berghe T, Grootjans S, Goossens V et al (2013) Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods 61:117–129.  https://doi.org/10.1016/j.ymeth.2013.02.011 Google Scholar
  22. 22.
    Vorobjev IA, Barteneva NS (2017) Multi-parametric imaging of cell heterogeneity in apoptosis analysis. Methods 112:105–123.  https://doi.org/10.1016/j.ymeth.2016.07.003 Google Scholar
  23. 23.
    Krysko DV, Vanden Berghe T, D’Herde K, Vandenabeele P (2008) Apoptosis and necrosis: detection, discrimination and phagocytosis. Methods 44:205–221.  https://doi.org/10.1016/j.ymeth.2007.12.001 Google Scholar
  24. 24.
    Belizário J, Vieira-Cordeiro L, Enns S (2015) Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediators Inflamm.  https://doi.org/10.1155/2015/128076 Google Scholar
  25. 25.
    Chen X, He W, Hu L et al (2016) Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res 26:1–14.  https://doi.org/10.1038/cr.2016.100 Google Scholar
  26. 26.
    Vanden Berghe T, Vanlangenakker N, Parthoens E et al (2010) Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ 17:922–930.  https://doi.org/10.1038/cdd.2009.184 Google Scholar
  27. 27.
    Broaddus VC, Yang L, Scavo LM et al (1996) Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species. J Clin Invest 98:2050–2059.  https://doi.org/10.1172/JCI119010 Google Scholar
  28. 28.
    Koopman G, Reutelingsperger CP, Kuijten GA et al (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84:1415–1420Google Scholar
  29. 29.
    Lecoeur H, Ledru E, Prévost MC, Gougeon ML (1997) Strategies for phenotyping apoptotic peripheral human lymphocytes comparing ISNT, annexin-V and 7-AAD cytofluorometric staining methods. J Immunol Methods 209:111–123.  https://doi.org/10.1016/S0022-1759(97)00138-5 Google Scholar
  30. 30.
    Jiang L, Tixeira R, Caruso S et al (2016) Monitoring the progression of cell death and the disassembly of dying cells by flow cytometry. Nat Protoc 11:655–663.  https://doi.org/10.1038/nprot.2016.028 Google Scholar
  31. 31.
    He S, Huang S, Shen Z (2016) Biomarkers for the detection of necroptosis. Cell Mol Life Sci 73:2177–2181.  https://doi.org/10.1007/s00018-016-2192-3 Google Scholar
  32. 32.
    Wallach D, Kang T-B, Dillon CP, Green DR (2016) Programmed necrosis in inflammation: toward identification of the effector molecules. Science 352:aaf2154–aaf2154.  https://doi.org/10.1126/science.aaf2154 Google Scholar
  33. 33.
    Krysko DV, D’Herde K, Vandenabeele P (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11(10):1709–1726.  https://doi.org/10.1007/s10495-006-9527-8 Google Scholar
  34. 34.
    Kroemer G, Galluzzi L, Vandenabeele P et al (2009) Classification of cell death 2009. Cell Death Differ 16:3–11.  https://doi.org/10.1038/cdd.2008.150 Google Scholar
  35. 35.
    Dzhagalov IL, Chen KG, Herzmark P, Robey EA (2013) Elimination of self-reactive T cells in the thymus: a timeline for negative selection. PLoS Biol 11(5):e1001566.  https://doi.org/10.1371/journal.pbio.1001566 Google Scholar
  36. 36.
    Elliott MR, Ravichandran KS (2010) Clearance of apoptotic cells: Implications in health and disease. J Cell Biol 189:1059–1070.  https://doi.org/10.1083/jcb.201004096 Google Scholar
  37. 37.
    Duan WR, Gamer DS, Williams SD et al (2003) Comparison of immunohistochemistry for activated caspase-3 and cleaved cytokeratin 18 with the TUNEL method for quantification of apoptosis in histological sections of PC-3 subcutaneous xenografts. J Pathol.  https://doi.org/10.1002/path.1289 Google Scholar
  38. 38.
    Mesa KR, Rompolas P, Zito G et al (2015) Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature 522:94–97.  https://doi.org/10.1038/nature14306 Google Scholar
  39. 39.
    Mayer CT, Mayer CT, Gazumyan A et al (2017) The microanatomic segregation of selection by apoptosis in the germinal center. Science 2602:1–14.  https://doi.org/10.1126/science.aao2602 Google Scholar
  40. 40.
    Garrod KR, Moreau HD, Garcia Z et al (2012) Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis. Cell Rep.  https://doi.org/10.1016/j.celrep.2012.10.015 Google Scholar
  41. 41.
    Bergsmedh A, Szeles A, Henriksson M et al (2001) Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 98:6407–6411.  https://doi.org/10.1073/pnas.101129998 Google Scholar
  42. 42.
    Ait-Oufella H, Pouresmail V, Simon T et al (2008) Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis. Arterioscler Thromb Vasc Biol.  https://doi.org/10.1161/ATVBAHA.108.169078 Google Scholar
  43. 43.
    Schrijvers DM, De Meyer GRY, Kockx MM et al (2005) Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol.  https://doi.org/10.1161/01.ATV.0000166517.18801.a7 Google Scholar
  44. 44.
    Seimon T, Tabas I (2009) Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res.  https://doi.org/10.1194/jlr.R800032-JLR200 Google Scholar
  45. 45.
    György B, Szabó TG, Pásztói M et al (2011) Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 68:2667–2688.  https://doi.org/10.1007/s00018-011-0689-3 Google Scholar
  46. 46.
    Baumann I, Kolowos W et al (2002) Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 46:191–201.  https://doi.org/10.1002/art.10027 Google Scholar
  47. 47.
    Caruso S, Poon IKH (2018) Apoptotic cell-derived extracellular vesicles: more than just debris. Front Immunol.  https://doi.org/10.3389/fimmu.2018.01486 Google Scholar
  48. 48.
    Jiang L, Tixeira R, Caruso S et al (2016) [Sup]Monitoring the progression of cell death and the disassembly of dying cells by flow cytometry. Nat Protoc 11:655–663.  https://doi.org/10.1038/nprot.2016.028 Google Scholar
  49. 49.
    Poon IKH, Chiu Y-H, Armstrong AJ et al (2014) Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature 507:329–334.  https://doi.org/10.1038/nature13147 Google Scholar
  50. 50.
    Zernecke A, Bidzhekov K, Noels H et al (2009) Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2:1–13.  https://doi.org/10.1126/scisignal.2000610 Google Scholar
  51. 51.
    Jiang L, Paone S, Caruso S et al (2017) Determining the contents and cell origins of apoptotic bodies by flow cytometry. Sci Rep 7:14444.  https://doi.org/10.1038/s41598-017-14305-z Google Scholar
  52. 52.
    Saraste A (1999) Morphologic criteria and detection of apoptosis. Herz 24:189–195.  https://doi.org/10.1007/BF03044961 Google Scholar
  53. 53.
    Nagata S, Suzuki J, Segawa K, Fujii T (2016) Exposure of phosphatidylserine on the cell surface. Cell Death Differ 23:952–961.  https://doi.org/10.1038/cdd.2016.7 Google Scholar
  54. 54.
    Van Engeland M, Nieland LJW, Ramaekers FCS et al (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31(1):1–9Google Scholar
  55. 55.
    Lane JD, Allan VJ, Woodman PG (2005) Active relocation of chromatin and endoplasmic reticulum into blebs in late apoptotic cells. J Cell Sci 118:4059–4071.  https://doi.org/10.1242/jcs.02529 Google Scholar
  56. 56.
    Croft DR, Coleman ML, Li S et al (2005) Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration. J Cell Biol 168:245–255.  https://doi.org/10.1083/jcb.200409049 Google Scholar
  57. 57.
    Osteikoetxea X, Balogh A, Szabó-Taylor K et al (2015) Improved characterization of EV preparations based on protein to lipid ratio and lipid properties. PLoS ONE 10(3):e0121184.  https://doi.org/10.1371/journal.pone.0121184 Google Scholar
  58. 58.
    Moss DK, Lane JD (2006) Microtubules: forgotten players in the apoptotic execution phase. Trends Cell Biol 16:330–338.  https://doi.org/10.1016/j.tcb.2006.05.005 Google Scholar
  59. 59.
    Hristov M, Erl W, Linder S, Weber PC (2004) Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood 104:2761.  https://doi.org/10.1182/blood-2003-10-3614 Google Scholar
  60. 60.
    Wickman GR, Julian L, Mardilovich K et al (2013) Blebs produced by actin-myosin contraction during apoptosis release damage-associated molecular pattern proteins before secondary necrosis occurs. Cell Death Differ 20:1293–1305.  https://doi.org/10.1038/cdd.2013.69 Google Scholar
  61. 61.
    Atkin-Smith GK, Paone S, Zanker DJ et al (2017) Isolation of cell type-specific apoptotic bodies by fluorescence-activated cell sorting. Sci Rep 7:39846.  https://doi.org/10.1038/srep39846 Google Scholar
  62. 62.
    van Ham TJ, Mapes J, Kokel D, Peterson RT (2010) Live imaging of apoptotic cells in zebrafish. FASEB J.  https://doi.org/10.1096/fj.10-161018 Google Scholar
  63. 63.
    Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. J Intern Med 258:479–517.  https://doi.org/10.1111/j.1365-2796.2005.01570.x Google Scholar
  64. 64.
    Tran HB, Ohlsson M, Beroukas D, et al (2002) Subcellular redistribution of La/SSB autoantigen during physiologic apoptosis in the fetal mouse heart and conduction system: a clue to the pathogenesis of congenital heart block. Arthritis Rheum 46:202–208.  https://doi.org/10.1002/art.10062 Google Scholar
  65. 65.
    Elmore SA, Dixon D, Hailey JR et al (2016) Recommendations from the INHAND Apoptosis/Necrosis Working Group. Toxicol Pathol 44:173–188.  https://doi.org/10.1177/0192623315625859 Google Scholar
  66. 66.
    Evans CJ, Aguilera RJ (2003) DNase II: genes, enzymes and function. Gene 322:1–15.  https://doi.org/10.1016/j.gene.2003.08.022 Google Scholar
  67. 67.
    Lee CS, Penberthy KK, Wheeler KM et al (2016) Boosting apoptotic cell clearance by colonic epithelial cells attenuates inflammation in vivo. Immunity 44:1–14.  https://doi.org/10.1016/j.immuni.2016.02.005 Google Scholar
  68. 68.
    Loo DT (2011) In situ detection of apoptosis by the TUNEL assay: an overview of techniques. In: Didenko V (ed) DNA Damage Detection In Situ, Ex Vivo, and In Vivo. Methods in Molecular Biology (Methods and Protocols), vol 682. Humana Press, Totowa.  https://doi.org/10.1007/978-1-60327-409-8_1
  69. 69.
    Berda-Haddad Y, Robert S, Salers P et al (2011) Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1. Proc Natl Acad Sci USA.  https://doi.org/10.1073/pnas.1116848108 Google Scholar
  70. 70.
    Lleo A, Zhang W, Mcdonald WH et al (2014) Shotgun proteomics: identification of unique protein profiles of apoptotic bodies from biliary epithelial cells. Hepatology.  https://doi.org/10.1002/hep.27230 Google Scholar
  71. 71.
    Berda-Haddad Y, Robert S, Salers P et al (2011) Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1. Proc Natl Acad Sci USA 108:20684–20689.  https://doi.org/10.1073/pnas.1116848108 Google Scholar
  72. 72.
    Crescitelli R, Lässer C, Szabó TG et al (2013) Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles.  https://doi.org/10.3402/jev.v2i0.20677 Google Scholar
  73. 73.
    Liu D, Kou X, Chen C et al (2018) Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res.  https://doi.org/10.1038/s41422-018-0070-2 Google Scholar
  74. 74.
    Guo SC, Tao SC, Dawn H (2018) Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles. J Extracell Vesicles 7:1508271.  https://doi.org/10.1080/20013078.2018.1508271 Google Scholar
  75. 75.
    Ravichandran KS (2010) Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 207:1807–1817.  https://doi.org/10.1084/jem.20101157 Google Scholar
  76. 76.
    Panaretakis T, Kepp O, Brockmeier U et al (2009) Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J 28:578–590.  https://doi.org/10.1038/emboj.2009.1 Google Scholar
  77. 77.
    Davies SP, Reynolds GM, Stamataki Z (2018) Clearance of apoptotic cells by tissue epithelia: a putative role for hepatocytes in liver efferocytosis. Front Immunol 9:1–15.  https://doi.org/10.3389/fimmu.2018.00044 Google Scholar
  78. 78.
    Fadok VA, Voelker DR, Campbell PA et al (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216Google Scholar
  79. 79.
    Savill J (1997) Recognition and phagocytosis of cells undergoing apoptosis. Br Med Bull 53:491–508.  https://doi.org/10.1093/oxfordjournals.bmb.a011626 Google Scholar
  80. 80.
    Bournazou I, Pound JD, Duffin R et al (2009) Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. J Clin Invest 119:20–32.  https://doi.org/10.1172/JCI36226 Google Scholar
  81. 81.
    Platt N, Fineran P (2015) Measuring the phagocytic activity of cells. Methods Cell Biol 126:287–304.  https://doi.org/10.1016/bs.mcb.2014.10.025 Google Scholar
  82. 82.
    Cunin P, Beauvillain C, Miot C et al (2016) Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses. Cell Death Dis 7:e2215.  https://doi.org/10.1038/cddis.2016.113 Google Scholar
  83. 83.
    Juncadella IJ, Kadl A, Sharma AK et al (2013) Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature 493:547–551.  https://doi.org/10.1038/nature11714 Google Scholar
  84. 84.
    Wang Y, Subramanian M, Yurdagul A et al (2017) Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell 171:331–345.e22.  https://doi.org/10.1016/j.cell.2017.08.041 Google Scholar
  85. 85.
    Lee CS, Penberthy KK, Wheeler KM et al (2016) Boosting apoptotic cell clearance by colonic epithelial cells attenuated inflammation in vivo. Immunity 44:1–14.  https://doi.org/10.1016/j.immuni.2016.02.005 Google Scholar
  86. 86.
    Tian L, Choi S-C, Lee H-N et al (2016) Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice. Cell Death Differ.  https://doi.org/10.1038/cdd.2015.161 Google Scholar
  87. 87.
    Han CZ, Juncadella IJ, Kinchen JM et al (2016) Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation. Nature.  https://doi.org/10.1038/nature20141 Google Scholar
  88. 88.
    Luo B, Gan W, Liu Z et al (2016) Erythropoeitin signaling in macrophages promotes dying cell clearance and immune tolerance. Immunity 44:1–16.  https://doi.org/10.1016/j.immuni.2016.01.002 Google Scholar
  89. 89.
    Trahtemberg U, Mevorach D (2009) Methods used to study apoptotic cell clearance. In: Krysko D.V., Vandenabeele P. (eds) Phagocytosis of Dying Cells: From Molecular Mechanisms to Human Diseases. Springer, Dordrecht.  https://doi.org/10.1007/978-1-4020-9293-0_8
  90. 90.
    Hanayama R, Tanaka M, Miwa K et al (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187.  https://doi.org/10.1038/417182a Google Scholar
  91. 91.
    Scott CC, Botelho RJ, Grinstein S (2003) Phagosome maturation: a few bugs in the system. J Membr Biol 193:137–152.  https://doi.org/10.1007/s00232-002-2008-2 Google Scholar
  92. 92.
    Poon IKH, Parish CR, Hulett MD (2010) Histidine-rich glycoprotein functions cooperatively with cell surface heparan sulfate on phagocytes to promote necrotic cell uptake. J Leukoc Biol 88:559–569.  https://doi.org/10.1189/jlb.0210087 Google Scholar
  93. 93.
    Wang Q, Ju X, Zhou Y, Chen K (2015) Necroptotic cells release find-me signal and are engulfed without proinflammatory cytokine production. Vitr Cell Dev Biol 51:1033–1039.  https://doi.org/10.1007/s11626-015-9926-7 Google Scholar
  94. 94.
    Nakaya M, Tajima M, Kosako H et al (2013) GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance. Nat Commun 4:1532.  https://doi.org/10.1038/ncomms2540 Google Scholar
  95. 95.
    Elliott MR, Chekeni FB, Trampont PC et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286.  https://doi.org/10.1038/nature08296 Google Scholar
  96. 96.
    Erazo T, Coppa A, Pujol A, Bu I (2014) PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans. Cell Death Dis.  https://doi.org/10.1038/cddis.2014.57 Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and Genetics, La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneAustralia

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