Skip to main content
SpringerLink
Log in

Results of Defective Clearance of Apoptotic Cells: Lessons from Knock-out Mouse Models

  • Chapter
Phagocytosis of Dying Cells: From Molecular Mechanisms to Human Diseases

Abstract

The current stupefying array of molecules associated with the celearance of cells undergoing apoptosis not only demonstrates complexity in the process but also suggests redundancy. The molecular complexity is rooted in multiple cellular events, including (1) multiple stages in the apoptosis programme, (2) multiple steps in the processes that culminate in engulfment and (3) multiple responses of different phagocytes. While there is almost relentless discovery of molecules that are implicated in these events, studies of knock-out mice are beginning to reveal their biological significance. Here we review these investigations, which demonstrate that, in certain circumstances, defective apoptotic-cell clearance can be associated with the pathogenesis of autoimmune disease. However, these studies also show that persistence of apoptotic cells as a consequence of defective clearance is not, of necessity, pro-inflammatory and immunostimulatory. Indeed, it appears that, under appropriate circumstances, persistent apoptotic cells may provide prolonged anti-inflammatory signals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albert ML, Pearce SFA, Francisco LM et al (1998) Immature dendritic cells phagocytose apoptotic cells via alpha(v)beta(5) and CD36, and cross-present antigens to cytotoxic T lymphocytes. JExp Med 188:1359–1368

    Article  CAS  Google Scholar 

  • Albert ML (2004) Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nat Rev Immunol 4:223–231

    Article  PubMed  CAS  Google Scholar 

  • Anderson HA, Englert R, Gursel I et al (2002) Oxidative stress inhibits the phagocytosis of apoptotic cells that have externalized phosphatidylserine. Cell Death Differ 9:616–625

    Article  PubMed  CAS  Google Scholar 

  • Arur S, Uche UE, Rezaul K et al (2003) Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev Cell 4:587–598

    Article  PubMed  CAS  Google Scholar 

  • Asano K, Miwa M, Miwa K et al (2004) Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice. J Exp Med 200:459–467

    Article  PubMed  CAS  Google Scholar 

  • Baumann I, Kolowos W, Voll RE 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

    Article  PubMed  Google Scholar 

  • Bennett MR, Gibson DF, Schwartz, SM et al (1995) Binding and phagocytosis of apoptotic vascular smooth muscle cells is mediated in part by exposure of phosphatidylserine. Circ Res 77:1136–1142

    PubMed  CAS  Google Scholar 

  • Bijl M, Horst G, Bijzet J et al (2003) Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte-derived macrophages. Arthritis Rheum 48:248–254

    Article  PubMed  CAS  Google Scholar 

  • Blander JM, Medzhitov R (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304:1014–1018

    Article  PubMed  CAS  Google Scholar 

  • Botto M, Dell’Agnola C, Bygrave AE et al (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19:56–59

    Article  PubMed  CAS  Google Scholar 

  • Bratton DL, Fadok VA, Richter DA et al (1997) Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. J Biol Chem272:26159–26165

    Article  PubMed  CAS  Google Scholar 

  • Bratton DL, Henson PM (2008) Apoptotic cell recognition: will the real phosphatidylserine receptor(s) please stand up? Curr Biol 18:R76–R79

    Article  CAS  Google Scholar 

  • Brown S, Heinisch I, Ross E et al (2002) Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 418:200

    Article  PubMed  CAS  Google Scholar 

  • Grainger DJ, Reckless J, McKilligin E (2004) Apolipoprotein E modulates clearance of apoptotic bodies in vitro and in vivo, resulting in a systemic pro-inflammatory state in apolipoprotein E-deficient mice. J Immunol 173:6366–6375

    PubMed  CAS  Google Scholar 

  • Gray M, Miles K, Salter D et al (2007) Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci U S A 104:14080–14085

    Article  PubMed  CAS  Google Scholar 

  • Gregory CD, Devitt A (1999) CD14 and apoptosis. Apoptosis 4:11–20

    Article  PubMed  CAS  Google Scholar 

  • Gregory CD (2000) CD14-dependent clearance of apoptotic cells: relevance to the immune system. Curr Opin Immunol 12:27–34

    Article  PubMed  CAS  Google Scholar 

  • Gregory CD, Devitt A (2004) The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically? Immunology 113:1–14

    Article  CAS  Google Scholar 

  • Grimsley C, Ravichandran KS (2003) Cues for apoptotic cell engulfment: eat-me, don’t eat-me and come-get-me signals. Trends Cell Biol 13:648–656

    Article  PubMed  CAS  Google Scholar 

  • Grimsley CM, Kinchen JM, Tosello-Trampont AC et al (2004) Dock180 andELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J Biol Chem 279:6087–6097

    Article  PubMed  CAS  Google Scholar 

  • Gumienny TL, Hengartner MO (2001) How the worm removes corpses: the nematode C. elegans as a model system to study engulfment. Cell Death Differ 8:564–568

    Article  PubMed  CAS  Google Scholar 

  • Hamon Y, Broccardo C, Chambenoit O et al (2000) ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2:399–406

    Article  PubMed  CAS  Google Scholar 

  • Hamon Y, Trompier D, Ma Z et al (2006) Cooperation between engulfment receptors: the case of ABCA1 and MEGF10. PLoS ONE 1: E120

    Article  PubMed  CAS  Google Scholar 

  • Hanayama R, Tanaka M, Miwa K et al (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187

    Article  PubMed  CAS  Google Scholar 

  • Hanayama R, Tanaka M, Miwa K et al (2004a) Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J Immunol 172:3876–3882

    CAS  Google Scholar 

  • Hanayama R, Tanaka M, Miyasaka K et al (2004b) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:1147–1150

    Article  CAS  Google Scholar 

  • Hanayama R, and Nagata S (2005) Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8. Proc Natl Acad Sci U S A 102:16886–16891

    Article  PubMed  CAS  Google Scholar 

  • Hart SP, Alexander KM, Dransfield I (2004a) Immune complexes bind preferentially to Fc gamma RIIA (CD32) on apoptotic neutrophils, leading to augmented phagocytosis by macrophages and release of pro-inflammatory cytokines. J Immunol 172:1882–1887

    CAS  Google Scholar 

  • Hart SP, Smith JR, Dransfield I (2004b) Phagocytosis of opsonized apoptotic cells: roles for ‘oldfashioned’ receptors for antibody and complement. Clin Exp Immunol 135:181–185

    Article  CAS  Google Scholar 

  • Hengartner MO (2001) Apoptosis: Corralling the corpses. Cell 104:325–328

    Article  PubMed  CAS  Google Scholar 

  • Henson PM, Hume DA (2006) Apoptotic cell removal in development and tissue homeostasis. Trends Immunol 27:244–250

    Article  PubMed  CAS  Google Scholar 

  • Hiramine C, Nakagawa T, Miyauchi A et al (1996) Thymic nurse cells as the site of thymocyte apoptosis and apoptotic cell clearance in the thymus of cyclophosphamide-treated mice. Lab Invest 75:185–201

    PubMed  CAS  Google Scholar 

  • Hoffmann PR, de Cathelineau AM, Ogden CA et al (2001) Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol 155:649–659

    Article  PubMed  CAS  Google Scholar 

  • Hristov M, Erl W, Linder S et al (2004) Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood 104:2761–2766

    Article  PubMed  CAS  Google Scholar 

  • Huynh ML, Fadok VA, Henson, PM (2002) Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 109:41–50

    PubMed  CAS  Google Scholar 

  • Iyoda T, Nagata K, Akashi M et al (2005) Neutrophils accelerate macrophage-mediated digestion of apoptotic cells in vivo as well as in vitro. J Immunol 175:3475–3483

    PubMed  CAS  Google Scholar 

  • Janeway CA (1989) Approaching the Asymptote -Evolution and Revolution in Immunology. Cold Spring Harb Symp Quant Biol 54:1–13

    PubMed  CAS  Google Scholar 

  • Kagan VE, Gleiss B, Tyurina YY et al (2002) A role for oxidative stress in apoptosis: Oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis. J Immunol 169:487–499

    PubMed  CAS  Google Scholar 

  • Kawagishi C, Kurosaka K, Watanabe N et al (2001) Cytokine production by macrophages in association with phagocytosis of etoposide-treated P388 cells in vitro and in vivo. Biochim Biophys Acta-Mol Cell Res 1541:221–230

    Article  CAS  Google Scholar 

  • Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  CAS  Google Scholar 

  • Kim SJ, Gershov D, Ma X et al (2003) Opsonization of apoptotic cells and its effect on macrophage and T cell immune responses. Ann N Y Acad Sci 987:68–78

    Article  PubMed  CAS  Google Scholar 

  • Kleinclauss F, Perruche S, Masson E et al (2006) Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion. Cell Death Differ 13:41–52

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi N, Karisola P, Pena-Cruz V et al (2007) TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27:927–940

    Article  PubMed  CAS  Google Scholar 

  • Kuchibhotla S, Vanegas D, Kennedy DJ et al (2008) Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II. Cardiovasc Res 78:185–196

    Article  PubMed  CAS  Google Scholar 

  • Kurosaka K, Takahashi M, and Kobayashi Y (2003a) Activation of extracellular signal-regulated kinase 1/2 is involved in production of CXC-chemokine by macrophages during phagocytosis of late apoptotic cells. Biochem Biophys Res Commun 306:1070–1074

    Article  CAS  Google Scholar 

  • Kurosaka K, Takahashi M, Watanabe N et al (2003b) Silent cleanup of very early apoptotic cells by macrophages. J Immunol 171:4672–4679

    CAS  Google Scholar 

  • Lacy-Hulbert A, Smith AM, Tissire H et al (2007) Ulcerative colitis and autoimmunity induced by loss of myeloid alpha v integrins. Proc Natl Acad Sci U S A 104:15823–15828

    Article  PubMed  CAS  Google Scholar 

  • Lauber K, Bohn E, Krober SM et al (2003) Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717–730

    Article  PubMed  CAS  Google Scholar 

  • Lawler J, Sunday M, Thibert V et al (1998) Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 101:982–992

    Article  PubMed  CAS  Google Scholar 

  • Lemke, G, and Lu, Q (2003) Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol 15:31–36

    Article  PubMed  CAS  Google Scholar 

  • Leonardi-Essmann F, Emig M, Kitamura Y et al (2005) Fractalkine-upregulated milk-fat globule EGF factor-8 protein in cultured rat microglia. J Neuroimmunol 160:92–101

    Article  PubMed  CAS  Google Scholar 

  • Li, MO Wan YY, Sanjabi S et al (2006) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24:99–146

    Article  PubMed  CAS  Google Scholar 

  • Lichanska AM, Browne CM, Henkel GW et al (1999) Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1. Blood 94:127–138

    PubMed  CAS  Google Scholar 

  • Lorimore SA, Coates PJ, Wright EG (2003) Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation. Oncogene 22:7058–7069

    Article  PubMed  CAS  Google Scholar 

  • Lucas M, Stuart LM, Savill J et al (2003) Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J Immunol 171:2610–2615

    PubMed  CAS  Google Scholar 

  • Lucas M, Stuart LM, Zhang A et al (2006) Requirements for apoptotic cell contact in regulation of macrophage responses. J Immunol 177:4047–4054

    PubMed  CAS  Google Scholar 

  • Martin SJ, Reutelingsperger CPM, McGahon AJ et al (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182:1545–1556

    Article  PubMed  CAS  Google Scholar 

  • McDonald PP, Fadok VA, Bratton D et al (1999) Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol 163:6164–6172

    PubMed  CAS  Google Scholar 

  • McPhillips K, Janssen WJ, Ghosh M et al (2007) TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic phospholipase A2 and oxidant-dependent mechanisms. J Immunol 178:8117–8126

    PubMed  CAS  Google Scholar 

  • Meagher LC, Savill JS, Baker A et al (1992) Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane-b2. J Leukocyte Biol 52:269–273

    PubMed  CAS  Google Scholar 

  • Medzhitov R, Janeway CA (1997) Innate immunity: The virtues of a nonclonal system of recognition. Cell 91:295–298

    Article  PubMed  CAS  Google Scholar 

  • Mevorach D, Mascarenhas JO, Gershov D et al (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188:2313–2320

    Article  PubMed  CAS  Google Scholar 

  • Miksa M, Amin D, Wu R et al (2007) Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages. Mol Med 13:553–560

    Article  PubMed  CAS  Google Scholar 

  • Mitchell DA, Pickering MC, Warren J et al (2002) C1q deficiency and autoimmunity: The effects of genetic background on disease expression. J Immunol 168:2538–2543

    PubMed  CAS  Google Scholar 

  • Miyanishi M, Tada K, Koike M et al (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–439

    Article  PubMed  CAS  Google Scholar 

  • Miyasaka K, Hanayama R, Tanaka M et al (2004) Expression of milk fat globule epidermal growth factor 8 in immature dendritic cells for engulfment of apoptotic cells. Eur J Immunol 34:1414–1422

    Article  PubMed  CAS  Google Scholar 

  • Morimoto K, Amano H, Sonoda F et al (2001) Alveolar macrophages that phagocytose apoptotic neutrophils produce hepatocyte growth factor during bacterial pneumonia in mice. Am J Respir Cell Mol Biol 24:608–615

    PubMed  CAS  Google Scholar 

  • Muhl H, Nold M, Chang JH et al (1999) Expression and release of chemokines associated with apoptotic cell death in human promonocytic U937 cells and peripheral blood mononuclear cells. Eur J Immunol 29:3225–3235

    Article  PubMed  CAS  Google Scholar 

  • Nakai Y, Shiratsuchi A, Manaka J et al (2005) Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. Exp Cell Res 309:137–148

    Article  PubMed  CAS  Google Scholar 

  • Nauta AJ, Trouw LA, Daha MR et al (2002) Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 32:1726–1736

    Article  PubMed  CAS  Google Scholar 

  • Nauta AJ, Raaschou-Jensen N, Roos A et al (2003) Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur J Immunol 33:2853–2863

    Article  PubMed  CAS  Google Scholar 

  • Navratil JS, Watkins SC, Wisnieski JJ et al (2001) The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. J Immunol 166:3231–3239

    PubMed  CAS  Google Scholar 

  • Norsworthy PJ, Fossati-Jimack L, Cortes-Hernandez J et al (2004) Murine CD93 (C1qRp) contributes to the removal of apoptotic cells in vivo but is not required for C1q-mediated enhancement of phagocytosis. J Immunol 172:3406–3414

    PubMed  CAS  Google Scholar 

  • Ogden CA, de Cathelineau A, Hoffmann PR et al (2001) C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 194:781–795

    Article  PubMed  CAS  Google Scholar 

  • Ogden CA, Pound JD, Batth BK et al (2005) Enhanced Apoptotic Cell Clearance Capacity and B Cell Survival Factor Production by IL-10-Activated Macrophages: Implications for Burkitt’s Lymphoma. J Immunol 174:3015–3023

    PubMed  CAS  Google Scholar 

  • Palaniyar N, Nadesalingam J, Clark H et al (2004) Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin. J Biol Chem 279:32728–32736

    Article  PubMed  CAS  Google Scholar 

  • Parente L, Solito E (2004) Annexin 1: more than an anti-phospholipase protein. Inflamm Res 53:125–132

    Article  PubMed  CAS  Google Scholar 

  • Park D, Tosello-Trampont AC, Elliott MR et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434

    Article  PubMed  CAS  Google Scholar 

  • Park SY, Jung MY, Kim HJ et al (2008) Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 15:192–201

    Article  PubMed  CAS  Google Scholar 

  • Pickering MC, Fischer S, Lewis MR et al (2001) Ultraviolet-radiation-induced keratinocyte apoptosis in C1q-deficient mice. J Invest Dermatol 117:52–58

    Article  PubMed  CAS  Google Scholar 

  • Platt N, Suzuki H, Kurihara Y et al (1996) Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc Natl Acad Sci U S A 93:12456–12460

    Article  PubMed  CAS  Google Scholar 

  • Platt N, Suzuki H, Kodama T et al (2000) Apoptotic thymocyte clearance in scavenger receptor class A-deficient mice is apparently normal. J Immunol 164:4861–4867

    PubMed  CAS  Google Scholar 

  • Quartier P, Potter PK, Ehrenstein MR et al (2005) Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol 35:252–260

    Article  PubMed  CAS  Google Scholar 

  • Sano H, Hsu DK, Apgar JR et al (2003) Critical role of galectin-3 in phagocytosis by macrophages. J Clin Invest 112:389–397

    PubMed  CAS  Google Scholar 

  • Santiago C, Ballesteros A, Martinez-Munoz L et al (2007) Structures of T cellimmunoglobulin mucin protein 4 show a metal-Ion-dependent ligand binding site where phosphatidylserine binds. Immunity 27:941–951

    Article  PubMed  CAS  Google Scholar 

  • Savill J, Dransfield I, Gregory C et al (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975

    Article  PubMed  CAS  Google Scholar 

  • Schiemann B, Gommerman JL, Vora K et al (2001) An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 293:2111–2114

    Article  PubMed  CAS  Google Scholar 

  • Scott RS, McMahon EJ, Pop SM et al (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207–211

    Article  PubMed  CAS  Google Scholar 

  • Shiratsuchi A, Watanabe I, Takeuchi O et al (2004) Inhibitory effect of toll-like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. J Immunol 172:2039–2047

    PubMed  CAS  Google Scholar 

  • Stern M, Savill J, Haslett C (1996) 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 149:911–921

    PubMed  CAS  Google Scholar 

  • Stuart LM, Takahashi K, Shi L et al (2005) Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J Immunol 174:3220–3226

    PubMed  CAS  Google Scholar 

  • Su HP, Nakada-Tsukui K, Tosello-Trampont AC et al (2002) Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP). J Biol Chem 277:11772–11779

    Article  PubMed  CAS  Google Scholar 

  • Surh CD, and Sprent J (1994) T-cell apoptosis detected in-situ during positive and negative selection in the thymus. Nature 372:100–103

    Article  PubMed  CAS  Google Scholar 

  • Svensson PA, Johnson MSC, Ling C et al (1999) Scavenger receptor class B type Iin the rat ovary: Possible role in high density lipoprotein cholesterol uptake and in the recognition of apoptotic granulosa cells. Endocrinology 140:2494–2500

    Article  PubMed  CAS  Google Scholar 

  • Szondy Z, Sarang Z, Molnar P et al (2003) Transglutaminase 2-/-mice reveal a phagocytosisassociated crosstalk between macrophages and apoptotic cells. Proc Natl Acad Sci U S A 100:7812–7817

    Article  PubMed  CAS  Google Scholar 

  • Taylor PR, Carugati A, Fadok VA et al (2000) A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192:359–366

    Article  PubMed  CAS  Google Scholar 

  • Tennant I, Pound J, Bournazou I et al (2008) Interaction of apoptotic cells with the innate immune system: exposure of apoptotic cell-associated molecular patterns (ACAMPs) that permit binding of anti-LPS antibodies and lactoferrin. Submitted

    Google Scholar 

  • Tosello-Trampont AC, Brugnera E, Ravichandran KS (2001) Evidence for a conserved role for CrkII and Rac in engulfment of apoptotic cells. J Biol Chem 276:13797–13802

    PubMed  CAS  Google Scholar 

  • Travis MA, Reizis B, Melton AC et al (2007) Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449:361–365

    Article  PubMed  CAS  Google Scholar 

  • Truman L, Ford C, Pazikowska M et al (2008) CX3CL1 (fractalkine) is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood. In press.

    Google Scholar 

  • Uchimura E, Watanabe N, Niwa O et al (2000) Transient infiltration of neutrophils into the thymus in association with apoptosis induced by whole-body X-irradiation. J Leukocyte Biol 67:780–784

    PubMed  CAS  Google Scholar 

  • Van Den Eijnde SM, Boshart L, Reutelingsperger CPM et al (1997) Phosphatidylserine plasma membrane asymmetry in vivo: A pancellular phenomenon which alters during apoptosis. Cell Death Differ 4:311–316

    Article  PubMed  CAS  Google Scholar 

  • Voll RE, Herrmann M, Roth EA et al (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351

    Article  PubMed  CAS  Google Scholar 

  • Weihua Z, Tsan R, Schroit AJ et al (2005) Apoptotic cells initiate endothelial cells prouting via electrostatic signalling. Cancer Res 65:11529–11535

    Article  PubMed  CAS  Google Scholar 

  • Wood W, Turmaine M, Weber R et al (2000) Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 127:5245–5252

    PubMed  CAS  Google Scholar 

  • Wu YC, Horvitz HR (1998) C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392:501–504

    Article  PubMed  CAS  Google Scholar 

  • Wyllie AH (1992) Apoptosis and the regulation of cell numbers in normal and neoplastic tissues-an overview. Cancer Metast Rev 11:95–103298

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK

    Christopher D. Gregory & John D. Pound

Authors
  1. Christopher D. Gregory
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John D. Pound
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. VIB Department for Molecular Biomedical Research, VIB and Ghent University, Technologiepark 927, 9052, Ghent, Belgium

    Dmitri V. Krysko M.D., Ph.D.  & Peter Vandenabeele Ph.D.  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Gregory, C.D., Pound, J.D. (2009). Results of Defective Clearance of Apoptotic Cells: Lessons from Knock-out Mouse Models. 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_9

Download citation

Publish with us

Policies and ethics

Search

Navigation