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PMID: 17591947 Published · ppublish English Journal Article Review

Immunological consequences of apoptotic cell phagocytosis.

The American journal of pathology ·Vol. 171 ·No. 1 ·2007-07-00 ·Pages 2-8

Erwig LP, Henson PM

Abstract

Cells undergo apoptosis in development, tissue homeostasis, and disease and are subsequently cleared by professional and nonprofessional phagocytes. There is now overwhelming evidence that phagocyte function is profoundly altered following apoptotic cell uptake, with consequences for the ensuing innate and adaptive immune response. Pathogens and tumors exploit the changes in macrophage function following apoptotic cell uptake. Here, we will outline the consequences of apoptotic cell phagocytosis and illustrate how apoptotic cells could be used to manipulate the immune response for therapeutic gain.

MeSH Terms
Apoptosis Autoimmunity Humans Immunity, Active Immunity, Innate Inflammation/immunology Lymphocyte Activation Macrophages/immunology Phagocytosis T-Lymphocytes/immunology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Erwig Lars-Peter
Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. mmd288@abdn.ac.uk
Henson Peter M
References (62)
62 references, click to expand
  1. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo.
    J Am Soc Nephrol. 2002 Oct;13(10):2497-507 PMID: 12239238
  2. Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease.
    Chest. 2006 Jun;129(6):1673-82 PMID: 16778289
  3. Negative selection--clearing out the bad apples from the T-cell repertoire.
    Nat Rev Immunol. 2003 May;3(5):383-91 PMID: 12766760
  4. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation.
    Cell. 2003 Oct 3;115(1):13-23 PMID: 14531999
  5. Silent cleanup of very early apoptotic cells by macrophages.
    J Immunol. 2003 Nov 1;171(9):4672-9 PMID: 14568942
  6. Heterogeneity of macrophage activation in anti-Thy-1.1 nephritis.
    Am J Pathol. 2003 Nov;163(5):2033-41 PMID: 14578202
  7. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave.
    Essays Biochem. 2003;39:105-17 PMID: 14585077
  8. Engulfment of apoptotic cells is negatively regulated by Rho-mediated signaling.
    J Biol Chem. 2003 Dec 12;278(50):49911-9 PMID: 14514696
  9. Innate immune discrimination of apoptotic cells: repression of proinflammatory macrophage transcription is coupled directly to specific recognition.
    J Immunol. 2004 Jan 15;172(2):880-9 PMID: 14707059
  10. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production.
    Mol Biol Cell. 2004 Mar;15(3):1089-100 PMID: 14668480
  11. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice.
    Science. 2004 May 21;304(5674):1147-50 PMID: 15155946
  12. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways.
    Dev Cell. 2004 Oct;7(4):491-501 PMID: 15469838
  13. Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2.
    J Leukoc Biol. 1992 Sep;52(3):269-73 PMID: 1522386
  14. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes.
    J Exp Med. 1994 Apr 1;179(4):1317-30 PMID: 7511686
  15. Human monocyte-derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis. Mediation by alpha v beta 3/CD36/thrombospondin recognition mechanism and lack of phlogistic response.
    Am J Pathol. 1996 Sep;149(3):911-21 PMID: 8780395
  16. Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.
    Transplantation. 1997 Apr 15;63(7):964-7 PMID: 9112348
  17. Immunosuppressive effects of apoptotic cells.
    Nature. 1997 Nov 27;390(6658):350-1 PMID: 9389474
  18. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
    J Clin Invest. 1998 Feb 15;101(4):890-8 PMID: 9466984
  19. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies.
    Nat Genet. 1998 May;19(1):56-9 PMID: 9590289
  20. Systemic exposure to irradiated apoptotic cells induces autoantibody production.
    J Exp Med. 1998 Jul 20;188(2):387-92 PMID: 9670050
  21. Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines.
    J Immunol. 1998 Aug 15;161(4):1983-8 PMID: 9712070
  22. Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils.
    Blood. 1999 Feb 15;93(4):1406-12 PMID: 9949185
  23. Cutting edge: differential effect of apoptotic versus necrotic tumor cells on macrophage antitumor activities.
    J Immunol. 1999 Aug 15;163(4):1730-2 PMID: 10438900
  24. Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth.
    FASEB J. 2004 Nov;18(14):1716-8 PMID: 15345697
  25. Transcriptional suppression of interleukin-12 gene expression following phagocytosis of apoptotic cells.
    Immunity. 2004 Nov;21(5):643-53 PMID: 15539151
  26. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient.
    Cell Death Differ. 2004 Dec;11(12):1258-64 PMID: 15375386
  27. Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice.
    J Cell Biol. 2004 Dec 20;167(6):1161-70 PMID: 15611337
  28. Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.
    J Exp Med. 2004 Dec 20;200(12):1539-45 PMID: 15596525
  29. Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype.
    J Immunol. 2005 Mar 15;174(6):3220-6 PMID: 15749852
  30. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate.
    Science. 2005 Mar 11;307(5715):1630-4 PMID: 15761154
  31. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17.
    Immunity. 2005 Mar;22(3):285-94 PMID: 15780986
  32. Phagocytosis: elegant complexity.
    Immunity. 2005 May;22(5):539-50 PMID: 15894272
  33. Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells.
    Nat Immunol. 2005 Jun;6(6):593-9 PMID: 15864309
  34. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells.
    Nat Cell Biol. 1999 Oct;1(6):362-8 PMID: 10559964
  35. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages.
    Nature. 2000 Jan 13;403(6766):199-203 PMID: 10646605
  36. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells.
    J Exp Med. 2000 Feb 7;191(3):423-34 PMID: 10662788
  37. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes.
    J Exp Med. 2000 Feb 7;191(3):435-44 PMID: 10662789
  38. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo.
    J Exp Med. 2000 Aug 7;192(3):359-66 PMID: 10934224
  39. Cell death in early neural development: beyond the neurotrophic theory.
    Trends Neurosci. 2000 Oct;23(10):454-8 PMID: 11006461
  40. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway.
    Int Immunol. 2000 Nov;12(11):1539-46 PMID: 11058573
  41. Phagocytosis and clearance of apoptotic cells is mediated by MER.
    Nature. 2001 May 10;411(6834):207-11 PMID: 11346799
  42. Alveolar macrophages that phagocytose apoptotic neutrophils produce hepatocyte growth factor during bacterial pneumonia in mice.
    Am J Respir Cell Mol Biol. 2001 May;24(5):608-15 PMID: 11350831
  43. Complement deficiencies in humans and animals: links to autoimmunity.
    Autoimmunity. 2006 Aug;39(5):367-78 PMID: 16923536
  44. Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12825-30 PMID: 16908865
  45. Clearance of apoptotic and necrotic cells and its immunological consequences.
    Apoptosis. 2006 Oct;11(10):1709-26 PMID: 16951923
  46. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis.
    Nat Med. 2006 Sep;12(9):1056-64 PMID: 16951685
  47. Decreased alveolar macrophage apoptosis is associated with increased pulmonary inflammation in a murine model of pneumococcal pneumonia.
    J Immunol. 2006 Nov 1;177(9):6480-8 PMID: 17056580
  48. Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus.
    Genes Immun. 2006 Oct;7(7):592-9 PMID: 16943797
  49. Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages.
    J Biol Chem. 2006 Dec 15;281(50):38376-84 PMID: 17056601
  50. Differential antigen processing by dendritic cell subsets in vivo.
    Science. 2007 Jan 5;315(5808):107-11 PMID: 17204652
  51. Resolution of inflammation: state of the art, definitions and terms.
    FASEB J. 2007 Feb;21(2):325-32 PMID: 17267386
  52. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation.
    J Clin Invest. 2002 Jan;109(1):41-50 PMID: 11781349
  53. Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation.
    J Immunol. 2002 Feb 15;168(4):1627-35 PMID: 11823490
  54. Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells.
    Clin Exp Immunol. 2002 Feb;127(2):220-5 PMID: 11876743
  55. Resolution of lung inflammation by CD44.
    Science. 2002 Apr 5;296(5565):155-8 PMID: 11935029
  56. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease.
    Blood. 2002 Jul 1;100(1):184-93 PMID: 12070026
  57. A role for CD36 in the regulation of dendritic cell function.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8750-5 PMID: 11447263
  58. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells.
    J Exp Med. 2001 Sep 17;194(6):781-95 PMID: 11560994
  59. Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects?
    Oncogene. 2001 Oct 25;20(48):7085-95 PMID: 11704832
  60. Apoptotic cells initiate endothelial cell sprouting via electrostatic signaling.
    Cancer Res. 2005 Dec 15;65(24):11529-35 PMID: 16357162
  61. Resolution of inflammation: the beginning programs the end.
    Nat Immunol. 2005 Dec;6(12):1191-7 PMID: 16369558
  62. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex.
    J Immunol. 2002 Oct 1;169(7):3978-86 PMID: 12244199
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2007.070135
Email
mmd288@abdn.ac.uk
Published
2007-07-00
Pages
2-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1941587
Subset
IM
Grants
Wellcome Trust · 073566 · United Kingdom
External Links
PubMed source DOI: 10.2353/ajpath.2007.070135 PMC Full Text View journal details
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