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Chapter 21 : Recognition and Removal of Apoptotic Cells

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Recognition and Removal of Apoptotic Cells, Page 1 of 2

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Abstract:

This chapter discusses the recognition of apoptotic cells by phagocytes, the mechanisms of apoptotic cell phagocytosis (efferocytosis), and some of the consequences of this recognition. It illustrates, with a few nonexhaustive examples, some of the possibilities for contribution of apoptotic cell recognition and/or its mechanisms to host-parasite interrelationships. In viable cells, phosphatidylserine (PS) is generally located on the inner leaflet of the plasma membrane, which is also enriched for phosphatidylethanolamine, whereas sphingomyelin is localized to the outer leaflet along with most of the phosphatidylcholine (PC). Under certain circumstances, activation of cells leads to increased flip-flop and, as a consequence, exposure of PS. Recent studies have implicated calreticulin as a ligand on apoptotic cells that can be recognized and contributes to their removal. The possibility that thrombospondin (TSP) can act as a glue to hold everything together is intriguing. The key feature of apoptotic cell removal is the ability of phagocytes to distinguish between living versus apoptosing, or dying, cells. The general conclusion from this discussion of receptors and bridge molecules is that recognition of apoptotic cells is a highly redundant process. Much work has been carried out on the signal pathways involved in uptake of apoptotic cells. The authors present a few examples to illustrate the potential for, and to raise questions about, other possible interactions between parasites and apoptotic cell recognition, ingestion, and consequences.

Citation: Henson P, Bratton D. 2009. Recognition and Removal of Apoptotic Cells, p 341-365. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch21

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Adaptive Immune System
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Macrophage Types
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Figures

Image of FIGURE 1
FIGURE 1

Macropinocytosis, phagocytosis, and uptake of apoptotic cells (efferocytosis). The proposed tether-and-tickle mechanism ( ) for apoptotic cell uptake is depicted with ingestion into spacious phagosomes. (With thanks to Aimee deCathelineau.)

Citation: Henson P, Bratton D. 2009. Recognition and Removal of Apoptotic Cells, p 341-365. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch21
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Image of FIGURE 2
FIGURE 2

Proposed mechanisms by which CD47 serves as a “don’t eat me” signal for viable cells, and which are inactivated when the cells become apoptotic. Ligation of SIRPα by CD47 on the viable cell activates inhibitory tyrosine phosphatases (SHPs) that block uptake signal pathways. Downregulation and/or redistribution of CD47 on apoptotic cells releases this inhibition and allows the uptake signaling to proceed. (From .)

Citation: Henson P, Bratton D. 2009. Recognition and Removal of Apoptotic Cells, p 341-365. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch21
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Image of FIGURE 3
FIGURE 3

Synopsis of possible signaling pathways associated with engulfment of apoptotic cells in and in mammals. PSRS, phosphatidylserine recognition structure, i.e., as yet unidentified phosphatidylserine receptors. (From .)

Citation: Henson P, Bratton D. 2009. Recognition and Removal of Apoptotic Cells, p 341-365. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch21
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References

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1. Aderem, A.,, and D. M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17:593623.
2. Akakura, S.,, S. Singh,, M. Spataro,, R. Akakura,, J. I. Kim,, M. L. Albert, and, R. B. Birge. 2004. The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Exp. Cell Res. 292:403416.
3. Albert, M. L.,, S. F. Pearce,, L. M. Francisco,, B. Sauter,, P. Roy,, R. L. Silverstein, and, N. Bhardwaj. 1998. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188:13591368.
4. Arur, S.,, U. E. Uche,, K. Rezaul,, M. Fong,, V. Scranton,, A. E. Cowan,, W. Mohler, and, D. K. Han. 2003. Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4:587598.
5. Asano, K.,, M. Miwa,, K. Miwa,, R. Hanayama,, H. Nagase,, S. Nagata, and, M. Tanaka. 2004. Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces auto-antibody production in mice. J. Exp. Med. 200:459467.
6. Awasaki, T.,, R. Tatsumi,, K. Takahashi,, K. Arai,, Y. Nakanishi,, R. Ueda, and, K. Ito. 2006. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 50:855867.
7. Balasubramanian, K.,, J. Chandra, and, A. J. Schroit. 1997. Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. J. Biol. Chem. 272:3111331117.
8. Balasubramanian, K.,, and A. J. Schroit. 1998. Characterization of phosphatidylserine-dependent beta2-glycoprotein I macrophage interactions. Implications for apoptotic cell clearance by phagocytes. J. Biol. Chem. 273:2927229277.
9. Bartl, M. M.,, T. Luckenbach,, O. Bergner,, O. Ullrich, and, C. Koch-Brandt. 2001. Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes. Exp. Cell Res. 271:130141.
10. Basu, S.,, R. J. Binder,, R. Suto,, K. M. Anderson, and, P. K. Srivastava. 2000. 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. 12:15391546.
11. Bayir, H.,, B. Fadeel,, M. J. Palladino,, E. Witasp,, I. V. Kurnikov,, Y. Y. Tyurina,, V. A. Tyurin,, A. A. Amoscato,, J. Jiang,, P. M. Kochanek,, S. T. DeKosky,, J. S. Greenberger,, A. A. Shvedova, and, V. E. Kagan. 2006. Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria. Biochim. Biophys. Acta 1757:648659.
12. Bergsmedh, A.,, A. Szeles,, M. Henriksson,, A. Bratt,, M. J. Folkman,, A. L. Spetz, and, L. Holmgren. 2001. Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc. Natl. Acad. Sci. USA 98:64076411.
13. Berwin, B.,, Y. Delneste,, R. V. Lovingood,, S. R. Post, and, S. V. Pizzo. 2004. SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J. Biol. Chem. 279:5125051257.
14. Bhatia, V. K.,, S. Yun,, V. Leung,, D. C. Grimsditch,, G. M. Benson,, M. B. Botto,, J. J. Boyle, and, D. O. Haskard. 2007. Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice. Am. J. Pathol. 170:416426.
15. Bijl, M.,, G. Horst,, J. Bijzet,, H. Bootsma,, P. C. Limburg, and, C. G. Kallenberg. 2003. Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte-derived macrophages. Arthritis Rheum. 48:248254.
16. Bluml, S.,, S. Kirchberger,, V. N. Bochkov,, G. Kronke,, K. Stuhlmeier,, O. Majdic,, G. J. Zlabinger,, W. Knapp,, B. R. Binder,, J. Stockl, and, N. Leitinger. 2005. Oxidized phospholipids negatively regulate dendritic cell maturation induced by TLRs and CD40. J. Immunol. 175:501508.
17. Bondanza, A.,, V. S. Zimmermann,, P. Rovere-Querini,, J. Turnay,, I. E. Dumitriu,, C. M. Stach,, R. E. Voll,, U. S. Gaipl,, W. Bertling,, E. Poschl,, J. R. Kalden,, A. A. Manfredi, and, M. Herrmann. 2004. Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J. Exp. Med. 200:11571165.
18. Boon, J. M.,, T. N. Lambert,, A. L. Sisson,, A. P. Davis, and, B. D. Smith. 2003. Facilitated phosphatidylserine (PS) flipflop and thrombin activation using a synthetic PS scramblase. J. Am. Chem. Soc. 125:81958201.
19. Borisenko, G. G.,, S. L. Iverson,, S. Ahlberg,, V. E. Kagan, and, B. Fadeel. 2004. Milk fat globule epidermal growth factor 8 (MFG-E8) binds to oxidized phosphatidylserine: implications for macrophage clearance of apoptotic cells. Cell Death Differ. 11:943945.
20. Bose, J.,, A. D. Gruber,, L. Helming,, S. Schiebe,, I. Wegener,, M. Hafner,, M. Beales,, F. Kontgen, and, A. Lengeling. 2004. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. J. Biol. 3:15.
21. Botto, M.,, C. Dell’Agnola,, A. E. Bygrave,, E. M. Thompson,, H. T. Cook,, F. Petry,, M. Loos,, P. P. Pandolfi, and, M. J. Walport. 1998. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19:5659.
22. Botto, M.,, and M. J. Walport. 2002. C1q, autoimmunity and apoptosis. Immunobiology 205:395406.
23. Bratton, D. L.,, V. A. Fadok,, D. A. Richter,, J. M. Kailey,, L. A. Guthrie, and, P. M. Henson. 1997. Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. J. Biol. Chem. 272:2615926165.
24. Brown, S.,, I. Heinisch,, E. Ross,, K. Shaw,, C. D. Buckley, and, J. Savill. 2002. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 418:200203.
25. Callahan, M. K.,, P. M. Popernack,, S. Tsutsui,, L. Truong,, R. A. Schlegel, and, A. J. Henderson. 2003. Phosphatidylserine on HIV envelope is a cofactor for infection of monocytic cells. J. Immunol. 170:48404845.
26. Caron, E.,, and A. Hall. 1998. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282:17171721.
27. Carrero, J. A.,, B. Calderon, and, E. R. Unanue. 2006. Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes. J. Exp. Med. 203:933940.
28. Carrero, J. A.,, and E. R. Unanue. 2006. Lymphocyte apoptosis as an immune subversion strategy of microbial pathogens. Trends Immunol. 27:497503.
29. Chang, B.,, Y. Chen,, Y. Zhao, and, R. K. Bruick. 2007. JMJD6 is a histone arginine demethylase. Science 318:444447.
30. Chang, M. K.,, C. J. Binder,, Y. I. Miller,, G. Subbanagounder,, G. J. Silverman,, J. A. Berliner, and, J. L. Witztum. 2004. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J. Exp. Med. 200:13591370.
31. Chang, M. K.,, C. J. Binder,, M. Torzewski, and, J. L. Witztum. 2002. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc. Natl. Acad. Sci. USA 99:1304313048.
32. Chen, X.,, K. Doffek,, S. L. Sugg, and, J. Shilyansky. 2004. Phosphatidylserine regulates the maturation of human dendritic cells. J. Immunol. 173:29852994.
33. Cikala, M.,, O. Alexandrova,, C. N. David,, M. Proschel,, B. Stiening,, P. Cramer, and, A. Bottger. 2004. The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity. BMC Cell Biol. 5:26.
34. Clark, H.,, N. Palaniyar,, P. Strong,, J. Edmondson,, S. Haw-good, and, K. B. Reid. 2002. Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J. Immunol. 169:28922899.
35. Cohen, P. L.,, R. Caricchio,, V. Abraham,, T. D. Camenisch,, J. C. Jennette,, R. A. Roubey,, H. S. Earp,, G. Matsushima, and, E. A. Reap. 2002. Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J. Exp. Med. 196:135140.
36. Conner, S. D.,, and S. L. Schmid. 2003. Regulated portals of entry into the cell. Nature 422:3744.
37. Cortes-Hernandez, J.,, L. Fossati-Jimack,, F. Petry,, M. Loos,, S. Izui,, M. J. Walport,, H. T. Cook, and, M. Botto. 2004. Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice. Eur. J. Immunol. 34:37133722.
38. Csomor, E.,, Z. Bajtay,, N. Sandor,, K. Kristof,, G. J. Arlaud,, S. Thiel, and, A. Erdei. 2007. Complement protein C1q induces maturation of human dendritic cells. Mol. Immunol. 44:33893397.
39. Cvetanovic, M.,, J. E. Mitchell,, V. Patel,, B. S. Avner,, Y. Su,, P. T. van der Saag,, P. L. Witte,, S. Fiore,, J. S. Levine, and, D. S. Ucker. 2006. Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity. J. Biol. Chem. 281:2005520067.
40. Dahl, M.,, A. K. Bauer,, M. Arredouani,, R. Soininen,, K. Tryggvason,, S. R. Kleeberger, and, L. Kobzik. 2007. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II. J. Clin. Investig. 117:757764.
41. Daleke, D. L. 2003. Regulation of transbilayer plasma membrane phospholipid asymmetry. J. Lipid Res. 44:233242.
42. Dalgaard, J.,, K. J. Beckstrom,, F. L. Jahnsen, and, J. E. Brinchmann. 2005. Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets. J. Leukoc. Biol. 77:689698.
43. deCathelineau, A. M.,, and P. M. Henson. 2003. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays Biochem. 39:105117.
44. de Freitas Balanco, J. M.,, M. E. Moreira,, A. Bonomo,, P. T. Bozza,, G. Amarante-Mendes,, C. Pirmez, and, M. A. Barcinski. 2001. Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity. Curr. Biol. 11:18701873.
45. de Souza, E. M.,, T. C. Araujo-Jorge,, C. Bailly,, A. Lansiaux,, M. M. Batista,, G. M. Oliveira, and, M. N. Soeiro. 2003. Host and parasite apoptosis following Trypanosoma cruzi infection in in vitro and in vivo models. Cell Tissue Res. 314:223235.
46. Devitt, A.,, O. D. Moffatt,, C. Raykundalia,, J. D. Capra,, D. L. Simmons, and, C. D. Gregory. 1998. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392:505509.
47. Devitt, A.,, K. G. Parker,, C. A. Ogden,, C. Oldreive,, M. F. Clay,, L. A. Melville,, C. O. Bellamy,, A. Lacy-Hulbert,, S. C. Gangloff,, S. M. Goyert, and, C. D. Gregory. 2004. Persistence of apoptotic cells without autoimmune disease or inflammation in CD14−/− mice. J. Cell Biol. 167:11611170.
48. Dillon, S. R.,, A. Constantinescu, and, M. S. Schlissel. 2001. Annexin V binds to positively selected B cells. J. Immunol. 166:5871.
49. Dini, L. 2000. Recognizing death: liver phagocytosis of apoptotic cells. Eur. J. Histochem. 44:217227.
50. Dini, L.,, A. Lentini,, G. D. Diez,, M. Rocha,, L. Falasca,, L. Serafino, and, F. Vidal-Vanaclocha. 1995. Phagocytosis of apoptotic bodies by liver endothelial cells. J. Cell Sci. 108(Pt 3):967973.
51. Donnelly, S.,, W. Roake,, S. Brown,, P. Young,, H. Naik,, P. Wordsworth,, D. A. Isenberg,, K. B. Reid, and, P. Eggleton. 2006. Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus. Arthritis Rheum. 54:15431556.
52. Duncan, J. L.,, M. M. LaVail,, D. Yasumura,, M. T. Matthes,, H. Yang,, N. Trautmann,, A. V. Chappelow,, W. Feng,, H. S. Earp,, G. K. Matsushima, and, D. Vollrath. 2003. An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest. Ophthalmol. Vis. Sci. 44:826838.
53. Eda, S.,, M. Yamanaka, and, M. Beppu. 2004. Carbohydrate-mediated phagocytic recognition of early apoptotic cells undergoing transient capping of CD43 glycoprotein. J. Biol. Chem. 279:59675974.
54. Edwards, J. L.,, E. J. Brown,, K. A. Ault, and, M. A. Apicella. 2001. The role of complement receptor 3 (CR3) in Neisseria gonorrhoeae infection of human cervical epithelia. Cell. Microbiol. 3:611622.
55. Elliott, J. I.,, A. Sardini,, J. C. Cooper,, D. R. Alexander,, S. Davanture,, G. Chimini, and, C. F. Higgins. 2006. Phosphatidylserine exposure in B lymphocytes: a role for lipid packing. Blood 108:16111617.
56. Elward, K.,, and P. Gasque. 2003. “Eat me” and “don’t eat me” signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol. Immunol. 40:8594.
57. Erwig, L. P.,, S. Gordon,, G. M. Walsh, and, A. J. Rees. 1999. Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils. Blood 93:14061412.
58. Erwig, L. P.,, K. A. McPhilips,, M. W. Wynes,, A. Ivetic,, A. J. Ridley, and, P. M. Henson. 2006. Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins. Proc. Natl. Acad. Sci. USA 103:1282512830.
59. Fadok, V. A.,, D. L. Bratton,, A. Konowal,, P. W. Freed,, J. Y. Westcott, and, P. M. Henson. 1998. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J. Clin. Investig. 101:890898.
60. Fadok, V. A.,, D. L. Bratton,, D. M. Rose,, A. Pearson,, R. A. Ezekewitz, and, P. M. Henson. 2000. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:8590.
61. Fadok, V. A.,, D. R. Voelker,, P. A. Campbell,, J. J. Cohen,, D. L. Bratton, and, P. M. Henson. 1992. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148:22072216.
62. Fan, X.,, S. Krahling,, D. Smith,, P. Williamson, and, R. A. Schlegel. 2004. Macrophage surface expression of annexins I and II in the phagocytosis of apoptotic lymphocytes. Mol. Biol. Cell 15:28632872.
63. Feng, H.,, Y. Zeng,, M. W. Graner, and, E. Katsanis. 2002. Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells. Blood 100:41084115.
64. Ferguson, T. A.,, and H. Kazama. 2005. Signals from dying cells: tolerance induction by the dendritic cell. Immunol. Res. 32:99108.
65. Finnemann, S. C.,, V. L. Bonilha,, A. D. Marmorstein, and, E. Rodriguez-Boulan. 1997. Phagocytosis of rod outer segments by retinal pigment epithelial cells requires alpha(v)beta5 integrin for binding but not for internalization. Proc. Natl. Acad. Sci. USA 94:1293212937.
66. Finnemann, S. C.,, and R. L. Silverstein. 2001. Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J. Exp. Med. 194:12891298.
67. Fisher, C. E.,, and S. E. Howie. 2006. The role of megalin (LRP-2/Gp330) during development. Dev. Biol. 296:279297.
68. Fleeton, M. N.,, N. Contractor,, F. Leon,, J. D. Wetzel,, T. S. Dermody, and, B. L. Kelsall. 2004. Peyer’s patch dendritic cells process viral antigen from apoptotic epithelial cells in the intestine of reovirus-infected mice. J. Exp. Med. 200:235245.
69. Franc, N. C.,, J. L. Dimarcq,, M. Lagueux,, J. Hoffmann, and, R. A. Ezekowitz. 1996. Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity 4:431443.
70. Frasch, S. C.,, P. M. Henson,, K. Nagaosa,, M. B. Fessler,, N. Borregaard, and, D. L. Bratton. 2004. Phospholipid flip-flop and phospholipid scramblase 1 (PLSCR1) co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils. J. Biol. Chem. 279:1762517633.
71. Freire-de-Lima, C. G.,, D. O. Nascimento,, M. B. Soares,, P. T. Bozza,, H. C. Castro-Faria-Neto,, F. G. de Mello,, G. A. DosReis, and, M. F. Lopes. 2000. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature 403:199203.
72. Freire-de-Lima, C. G.,, Y. Q. Xiao,, S. J. Gardai,, D. L. Bratton,, W. P. Schiemann, and, P. M. Henson. 2006. 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. 281:3837638384.
73. Gaipl, U. S.,, L. E. Munoz,, G. Grossmayer,, K. Lauber,, S. Franz,, K. Sarter,, R. E. Voll,, T. Winkler,, A. Kuhn,, J. Kalden,, P. Kern, and, M. Herrmann. 2007. Clearance deficiency and systemic lupus erythematosus (SLE). J. Autoimmun. 28:114121.
74. Gaipl, U. S.,, A. Sheriff,, S. Franz,, L. E. Munoz,, R. E. Voll,, J. R. Kalden, and, M. Herrmann. 2006. Inefficient clearance of dying cells and autoreactivity. Curr. Top. Microbiol. Immunol. 305:161176.
75. Galan, J. E. 2001. Salmonella interactions with host cells: type III secretion at work. Annu. Rev. Cell Dev. Biol. 17:5386.
76. Gardai, S. J.,, D. L. Bratton,, C. A. Ogden, and, P. M. Henson. 2006. Recognition ligands on apoptotic cells: a perspective. J. Leukoc. Biol. 79:896903.
77. Gardai, S. J.,, K. A. McPhillips,, S. C. Frasch,, W. J. Janssen,, A. Starefeldt,, J. E. Murphy-Ullrich,, D. L. Bratton,, P. A. Oldenborg,, M. Michalak, and, P. M. Henson. 2005. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 123:321334.
78. Gardai, S. J.,, Y. Q. Xiao,, M. Dickinson,, J. A. Nick,, D. R. Voelker,, K. E. Greene, and, P. M. Henson. 2003. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 115:1323.
79. Garlatti, V.,, N. Belloy,, L. Martin,, M. Lacroix,, M. Matsushita,, Y. Endo,, T. Fujita,, J. C. Fontecilla-Camps,, G. J. Arlaud,, N. M. Thielens, and, C. Gaboriaud. 2007. Structural insights into the innate immune recognition specificities of L- and H-ficolins. EMBO J. 26:623633.
80. Gebska, M. A.,, I. Titley,, H. F. Paterson,, R. M. Morilla,, D. C. Davies,, A. M. Gruszka-Westwood,, V. V. Kakkar,, S. Eccles, and, M. F. Scully. 2002. High-affinity binding sites for heparin generated on leukocytes during apoptosis arise from nuclear structures segregated during cell death. Blood 99:22212227.
81. Gershov, D.,, S. Kim,, N. Brot, and, K. B. Elkon. 2000. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J. Exp. Med. 192:13531364.
82. Ghebrehiwet, B. 1989. Functions associated with the C1q receptor. Behring Inst. Mitt. July:204215.
83. Ghebrehiwet, B.,, and E. I. Peerschke. 2004. Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus. Curr. Dir. Autoimmun. 7:8797.
84. Giles, K. M.,, K. Ross,, A. G. Rossi,, N. A. Hotchin,, C. Haslett, and, I. Dransfield. 2001. Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic cells is associated with reduced p130Cas expression, loss of paxillin/pyk2 phosphorylation, and high levels of active Rac. J. Immunol. 167:976986.
85. Gonias, S. L.,, L. Wu, and, A. M. Salicioni. 2004. Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteome. Thromb. Haemost. 91:10561064.
86. Greenaway, J.,, J. Lawler,, R. Moorehead,, P. Bornstein,, J. Lamarre, and, J. Petrik. 2007. Thrombospondin-1 inhibits VEGF levels in the ovary directly by binding and internalization via the low density lipoprotein receptor-related protein-1 (LRP-1). J. Cell. Physiol. 210:807818.
87. Greenberg, M. E.,, M. Sun,, R. Zhang,, M. Febbraio,, R. Silverstein, and, S. L. Hazen. 2006. Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J. Exp. Med. 203:261325.
88. Gregory, C. D.,, A. Devitt, and, O. Moffatt. 1998. Roles of ICAM-3 and CD14 in the recognition and phagocytosis of apoptotic cells by macrophages. Biochem. Soc. Trans. 26:644649.
89. Griffin, F. M., Jr.,, J. A. Griffin,, J. E. Leider, and, S. C. Silverstein. 1975. Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane. J. Exp. Med. 142:12631282.
90. Hafizi, S.,, and B. Dahlback. 2006. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. FEBS J. 273:52315344.
91. Hall, S. E.,, J. S. Savill,, P. M. Henson, and, C. Haslett. 1994. Apoptotic neutrophils are phagocytosed by fibroblasts with participation of the fibroblast vitronectin receptor and involvement of a mannose/fucose-specific lectin. J. Immunol. 153:32183227.
92. Hamon, Y.,, C. Broccardo,, O. Chambenoit,, M. F. Luciani,, F. Toti,, S. Chaslin,, J. M. Freyssinet,, P. F. Devaux,, J. McNeish,, D. Marguet, and, G. Chimini. 2000. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat. Cell Biol. 2:399406.
93. Hanayama, R.,, K. Miyasaka,, M. Nakaya, and, S. Nagata. 2006. MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure. Curr. Dir. Autoimmun. 9:162172.
94. Hanayama, R.,, M. Tanaka,, K. Miwa, and, S. Nagata. 2004a. Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J. Immunol. 172:38763882.
95. Hanayama, R.,, M. Tanaka,, K. Miyasaka,, K. Aozasa,, M. Koike,, Y. Uchiyama, and, S. Nagata. 2004b. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:11471150.
96. Harshyne, L. A.,, M. I. Zimmer,, S. C. Watkins, and, S. M. Barratt-Boyes. 2003. A role for class A scavenger receptor in dendritic cell nibbling from live cells. J. Immunol. 170:23022309.
97. Hart, J. P.,, M. D. Gunn, and, S. V. Pizzo. 2004. A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens. J. Immunol. 172:7078.
98. Hart, S. P.,, G. J. Dougherty,, C. Haslett, and, I. Dransfield. 1997. CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages. J. Immunol. 159:919925.
99. Hashimoto, Y.,, T. Moki,, T. Takizawa,, A. Shiratsuchi, and, Y. Nakanishi. 2007. Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol. 178:24482457.
100. Haslett, C.,, J. S. Savill,, M. K. Whyte,, M. Stern,, I. Dransfield, and, L. C. Meagher. 1994. Granulocyte apoptosis and the control of inflammation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 345:327333.
101. Heasman, S. J.,, K. M. Giles,, C. Ward,, A. G. Rossi,, C. Haslett, and, I. Dransfield. 2003. Glucocorticoid-mediated regulation of granulocyte apoptosis and macrophage phagocytosis of apoptotic cells: implications for the resolution of inflammation. J. Endocrinol. 178:2936.
102. Hildeman, D. A.,, T. Mitchell,, T. K. Teague,, P. Henson,, B. J. Day,, J. Kappler, and, P. C. Marrack. 1999. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 10:735744.
103. Hirano, K.,, Y. Miki,, Y. Hirai,, R. Sato,, T. Itoh,, A. Hayashi,, M. Yamanaka,, S. Eda, and, M. Beppu. 2005. A multifunctional shuttling protein nucleolin is a macrophage receptor for apoptotic cells. J. Biol. Chem. 280:3928439293.
104. Hoffmann, P. R.,, A. M. deCathelineau,, C. A. Ogden,, Y. Leverrier,, D. L. Bratton,, D. L. Daleke,, A. J. Ridley,, V. A. Fadok, and, P. M. Henson. 2001. Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J. Cell Biol. 155:649659.
105. Hoffmann, P. R.,, J. A. Kench,, A. Vondracek,, E. Kruk,, D. L. Daleke,, M. Jordan,, P. Marrack,, P. M. Henson, and, V. A. Fadok. 2005. Interaction between phosphatidylserine and the phosphatidylserine receptor inhibits immune responses in vivo. J. Immunol. 174:13931404.
106. Holmgren, L.,, A. Szeles,, E. Rajnavolgyi,, J. Folkman,, G. Klein,, I. Ernberg, and, K. I. Falk. 1999. Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood 93:39563963.
107. Hong, J. R.,, G. H. Lin,, C. J. Lin,, W. P. Wang,, C. C. Lee,, T. L. Lin, and, J. L. Wu. 2004. Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish. Development 131:54175427.
108. Huang, Y. M.,, J. S. Yang,, L. Y. Xu,, H. Link, and, B. G. Xiao. 2000. Autoantigen-pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats. Clin. Exp. Immunol. 122:437444.
109. Huynh, M. L.,, V. A. Fadok, and, P. M. Henson. 2002. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J. Clin. Investig. 109:4150.
110. Ishimoto, Y.,, K. Ohashi,, K. Mizuno, and, T. Nakano. 2000. Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J. Biochem. 127:411417.
111. Iyoda, T.,, S. Shimoyama,, K. Liu,, Y. Omatsu,, Y. Akiyama,, Y. Maeda,, K. Takahara,, R. M. Steinman, and, K. Inaba. 2002. The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J. Exp. Med. 195:12891302.
112. Jensen, M. L.,, C. Honore,, T. Hummelshoj,, B. E. Hansen,, H. O. Madsen, and, P. Garred. 2007. Ficolin-2 recognizes DNA and participates in the clearance of dying host cells. Mol. Immunol. 44:856865.
113. Kagan, V. E.,, B. Gleiss,, Y. Y. Tyurina,, V. A. Tyurin,, C. Elenstrom-Magnusson,, S. X. Liu,, F. B. Serinkan,, A. Arroyo,, J. Chandra,, S. Orrenius, and, B. Fadeel. 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. 169:487499.
114. Kawagishi, C.,, K. Kurosaka,, N. Watanabe, and, Y. Kobayashi. 2001. Cytokine production by macrophages in association with phagocytosis of etoposide-treated P388 cells in vitro and in vivo. Biochim. Biophys. Acta 1541:221230.
115. Kim, S. J.,, D. Gershov,, X. Ma,, N. Brot, and, K. B. Elkon. 2002. I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation. J. Exp. Med. 196:655665.
116. Kim, S. J.,, D. Gershov,, X. Ma,, N. Brot, and, K. B. Elkon. 2003. Opsonization of apoptotic cells and its effect on macrophage and T cell immune responses. Ann. N. Y. Acad. Sci. 987:6878.
117. Kinchen, J. M.,, J. Cabello,, D. Klingele,, K. Wong,, R. Feichtinger,, H. Schnabel,, R. Schnabel, and, M. O. Hengartner. 2005. Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature 434:9399.
118. Kishore, U.,, T. J. Greenhough,, P. Waters,, A. K. Shrive,, R. Ghai,, M. F. Kamran,, A. L. Bernal,, K. B. Reid,, T. Madan, and, T. Chakraborty. 2006. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol. Immunol. 43:12931315.
119. Kobayashi, N.,, P. Karisola,, V. Pena-Cruz,, D. M. Dorfman,, M. Jinushi,, S. E. Umetsu,, M. J. Butte,, H. Nagumo,, I. Chernova,, B. Zhu,, A. H. Sharpe,, S. Ito,, G. Dranoff,, G. G. Kaplan,, J. M. Casasnovas,, D. T. Umetsu,, R. H. Dekruyff, and, G. J. Freeman. 2007. TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27:927940.
120. Koizumi, S.,, Y. Shigemoto-Mogami,, K. Nasu-Tada,, Y. Shinozaki,, K. Ohsawa,, M. Tsuda,, B. V. Joshi,, K. A. Jacobson,, S. Kohsaka, and, K. Inoue. 2007. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446:10911095.
121. Korb, L. C.,, and J. M. Ahearn. 1997. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 158:45254528.
122. Kovacsovics, T.,, J. Tschopp,, A. Kress, and, H. Isliker. 1985. Antibody-independent activation of C1, the first component of complement, by cardiolipin. J. Immunol. 135:26952700.
123. Krieser, R. J.,, F. E. Moore,, D. Dresnek,, B. J. Pellock,, R. Patel,, A. Huang,, C. Brachmann, and, K. White. 2007. The Drosophila homolog of the putative phosphatidylserine receptor functions to inhibit apoptosis. Development 134:24072414.
124. Krysko, D. V.,, K. D’Herde, and, P. Vandenabeele. 2006a. Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11:17091726.
125. Krysko, D. V.,, G. Denecker,, N. Festjens,, S. Gabriels,, E. Parthoens,, K. D’Herde, and, P. Vandenabeele. 2006b. Macrophages use different internalization mechanisms to clear apoptotic and necrotic cells. Cell Death Differ. 13:20112022.
126. Kunisaki, Y.,, S. Masuko,, M. Noda,, A. Inayoshi,, T. Sanui,, M. Harada,, T. Sasazuki, and, Y. Fukui. 2004. Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor. Blood 103:33623364.
127. Kuraishi, T.,, J. Manaka,, M. Kono,, H. Ishii,, N. Yamamoto,, K. Koizumi,, A. Shiratsuchi,, B. L. Lee,, H. Higashida, and, Y. Nakanishi. 2007. Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila. Exp. Cell Res. 313:500510.
128. Kuraya, M.,, Z. Ming,, X. Liu,, M. Matsushita, and, T. Fujita. 2005. Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activation. Immunobiology 209:689697.
129. Lange, Y.,, J. Ye, and, T. L. Steck. 2007. Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry 46:22332238.
130. Laskay, T.,, G. van Zandbergen, and, W. Solbach. 2003. Neutrophil granulocytes—Trojan horses for Leishmania major and other intracellular microbes? Trends Microbiol. 11:210214.
131. Lauber, K.,, E. Bohn,, S. M. Krober,, Y. J. Xiao,, S. G. Blumenthal,, R. K. Lindemann,, P. Marini,, C. Wiedig,, A. Zobywalski,, S. Baksh,, Y. Xu,, I. B. Autenrieth,, K. Schulze-Osthoff,, C. Belka,, G. Stuhler, and, S. Wesselborg. 2003. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717730.
132. Leverrier, Y.,, and A. J. Ridley. 2001. Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages. Curr. Biol. 11:195199.
133. Li, M. O.,, M. R. Sarkisian,, W. Z. Mehal,, P. Rakic, and, R. A. Flavell. 2003. Phosphatidylserine receptor is required for clearance of apoptotic cells. Science 302:15601563.
134. Li, W.,, and N. E. Baker. 2007. Engulfment is required for cell competition. Cell 129:12151225.
135. Lima, R. G.,, L. Moreira,, J. Paes-Leme,, V. Barreto-de-Souza,, H. C. Castro-Faria-Neto,, P. T. Bozza, and, D. C. Bou-Habib. 2006. Interaction of macrophages with apoptotic cells enhances HIV Type 1 replication through PGE2, PAF, and vitronectin receptor. AIDS Res. Hum. Retroviruses 22:763769.
136. Lin, H.,, and D. O. Clegg. 1998. Integrin alphavbeta5 participates in the binding of photoreceptor rod outer segments during phagocytosis by cultured human retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 39:17031712.
137. Liu, G.,, C. Wu,, Y. Wu, and, Y. Zhao. 2006. Phagocytosis of apoptotic cells and immune regulation. Scand. J. Immunol. 64:19.
138. Liu, Y.,, J. M. Cousin,, J. Hughes,, J. Van Damme,, J. R. Seckl,, C. Haslett,, I. Dransfield,, J. Savill, and, A. G. Rossi. 1999. Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J. Immunol. 162:36393646.
139. Lu, Q.,, and G. Lemke. 2001. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293:306311.
140. Lucas, M.,, L. M. Stuart,, J. Savill, and, A. Lacy-Hulbert. 2003. Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J. Immunol. 171:26102615.
141. Maderna, P.,, D. C. Cottell,, G. Berlasconi,, N. A. Petasis,, H. R. Brady, and, C. Godson. 2002. Lipoxins induce actin reorganization in monocytes and macrophages but not in neutrophils: differential involvement of rho GTPases. Am. J. Pathol. 160:22752283.
142. Manaka, J.,, T. Kuraishi,, A. Shiratsuchi,, Y. Nakai,, H. Higashida,, P. Henson, and, Y. Nakanishi. 2004. Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. J. Biol. Chem. 279:4846648476.
143. Manfredi, A. A.,, P. Rovere,, S. Heltai,, G. Galati,, G. Nebbia,, A. Tincani,, G. Balestrieri, and, M. G. Sabbadini. 1998. Apoptotic cell clearance in systemic lupus erythematosus. II. Role of beta2-glycoprotein I. Arthritis Rheum. 41:215223.
144. Marth, T.,, and B. L. Kelsall. 1997. Regulation of interleukin-12 by complement receptor 3 signaling. J. Exp. Med. 185:19871995.
145. Martin, S. J.,, C. P. Reutelingsperger,, A. J. McGahon,, J. A. Rader,, R. C. van Schie,, D. M. LaFace, and, D. R. Green. 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. 182:15451556.
146. McPhillips, K.,, W. J. Janssen,, M. Ghosh,, A. Byrne,, S. Gardai,, L. Remigio,, D. L. Bratton,, J. L. Kang, and, P. Henson. 2007. TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic phospholipase A2 and oxidant-dependent mechanisms. J. Immunol. 178:81178126.
147. Meagher, L. C.,, J. S. Savill,, A. Baker,, R. W. Fuller, and, C. Haslett. 1992. Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. J. Leukoc. Biol. 52:2692-73.
148. Mevorach, D.,, J. O. Mascarenhas,, D. Gershov, and, K. B. Elkon. 1998. Complement-dependent clearance of apoptotic cells by human macrophages. J. Exp. Med. 188:23132320.
149. Miller, Y. I.,, S. Viriyakosol,, C. J. Binder,, J. R. Feramisco,, T. N. Kirkland, and, J. L. Witztum. 2003. Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 278:15611568.
150. Mitchell, J. E.,, M. Cvetanovic,, N. Tibrewal,, V. Patel,, O. R. Colamonici,, M. O. Li,, R. A. Flavell,, J. S. Levine,, R. B. Birge, and, D. S. Ucker. 2006. The presumptive phosphatidylserine receptor is dispensable for innate anti-inflammatory recognition and clearance of apoptotic cells. J. Biol. Chem. 281:57185725.
151. Mitchell, S.,, G. Thomas,, K. Harvey,, D. Cottell,, K. Reville,, G. Berlasconi,, N. A. Petasis,, L. Erwig,, A. J. Rees,, J. Savill,, H. R. Brady, and, C. Godson. 2002. 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. 13:24972507.
152. Mitra, P.,, C. A. Oskeritzian,, S. G. Payne,, M. A. Beaven,, S. Milstien, and, S. Spiegel. 2006. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl. Acad. Sci. USA 103:1639416399.
153. Miyanishi, M.,, K. Tada,, M. Koike,, Y. Uchiyama,, T. Kitamura, and, S. Nagata. 2007. Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435439.
154. Mold, C.,, R. Baca, and, T. W. Du Clos. 2002. Serum amyloid P component and C-reactive protein opsonize apoptotic cells for phagocytosis through Fcgamma receptors. J. Autoimmun. 19:147154.
155. Morelli, A. E.,, A. T. Larregina,, W. J. Shufesky,, A. F. Zahorchak,, A. J. Logar,, G. D. Papworth,, Z. Wang,, S. C. Watkins,, L. D. Falo, Jr., and, A. W. Thomson. 2003. Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. Blood 101:611620.
156. Munoz, L. E.,, S. Franz,, F. Pausch,, B. Furnrohr,, A. Sheriff,, B. Vogt,, P. M. Kern,, W. Baum,, C. Stach,, D. von Laer,, B. Brachvogel,, E. Poschl,, M. Herrmann, and, U. S. Gaipl. 2007a. The influence on the immunomodulatory effects of dying and dead cells of Annexin V. J. Leukoc. Biol. 81:614.
157. Munoz, L. E.,, B. Frey,, F. Pausch,, W. Baum,, R. B. Mueller,, B. Brachvogel,, E. Poschl,, F. Rodel,, K. von der Mark,, M. Herrmann, and, U. S. Gaipl. 2007b. The role of annexin A5 in the modulation of the immune response against dying and dead cells. Curr. Med. Chem. 14:271277.
158. Murphy, J. E.,, D. Tacon,, P. R. Tedbury,, J. M. Hadden,, S. Knowling,, T. Sawamura,, M. Peckham,, S. E. Phillips,, J. H. Walker, and, S. Ponnambalam. 2006. LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells. Biochem. J. 393:107115.
159. Nagaosa, K.,, A. Shiratsuchi, and, Y. Nakanishi. 2003. Concomitant induction of apoptosis and expression of monocyte chemoattractant protein-1 in cultured rat luteal cells by nuclear factor-kappaB and oxidative stress. Dev. Growth Differ. 45:351359.
160. Nandrot, E. F.,, Y. Kim,, S. E. Brodie,, X. Huang,, D. Sheppard, and, S. C. Finnemann. 2004. Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J. Exp. Med. 200:15391545.
161. Navratil, J. S.,, S. C. Watkins,, J. J. Wisnieski, and, J. M. Ahearn. 2001. The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. J. Immunol. 166:32313239.
162. Neumann, H.,, and K. Takahashi. 2007. Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis. J. Neuroimmunol. 184:9299.
163. Obeid, M.,, A. Tesniere,, F. Ghiringhelli,, G. M. Fimia,, L. Apetoh,, J. L. Perfettini,, M. Castedo,, G. Mignot,, T. Panaretakis,, N. Casares,, D. Metivier,, N. Larochette,, P. van Endert,, F. Ciccosanti,, M. Piacentini,, L. Zitvogel, and, G. Kroemer. 2007. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 13:5461.
164. Ogden, C. A.,, A. deCathelineau,, P. R. Hoffmann,, D. Bratton,, B. Ghebrehiwet,, V. A. Fadok, and, P. M. Henson. 2001. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J. Exp. Med. 194:781795.
165. Ogden, C. A.,, J. D. Pound,, B. K. Batth,, S. Owens,, I. Johannessen,, K. Wood, and, C. D. Gregory. 2005. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt’s lymphoma. J. Immunol. 174:30153023.
166. Oka, K.,, T. Sawamura,, K. Kikuta,, S. Itokawa,, N. Kume,, T. Kita, and, T. Masaki. 1998. Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells. Proc. Natl. Acad. Sci. USA 95:95359540.
167. Okada, H.,, and T. W. Mak. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 4:592603.
168. Orr, A. W.,, C. E. Pedraza,, M. A. Pallero,, C. A. Elzie,, S. Goicoechea,, D. K. Strickland, and, J. E. Murphy-Ullrich. 2003. Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly. J. Cell Biol. 161:11791189.
169. Palaniyar, N.,, H. Clark,, J. Nadesalingam,, S. Hawgood, and, K. B. Reid. 2003. Surfactant protein D binds genomic DNA and apoptotic cells, and enhances their clearance, in vivo. Ann. N. Y. Acad. Sci. 1010:471475.
170. Palaniyar, N.,, J. Nadesalingam,, H. Clark,, M. J. Shih,, A. W. Dodds, and, K. B. Reid. 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. 279:3272832736.
171. Park, D.,, A. C. Tosello-Trampont,, M. R. Elliott,, M. Lu,, L. B. Haney,, Z. Ma,, A. L. Klibanov,, J. W. Mandell, and, K. S. Ravichandran. 2007. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430434.
172. Park, S. Y.,, M. Y. Jung,, H. J. Kim,, S. J. Lee,, S. Y. Kim,, B. H. Lee,, T. H. Kwon,, R. W. Park, and, I. S. Kim. 2008. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 15:192201.
173. Peerschke, E. I.,, K. B. Reid, and, B. Ghebrehiwet. 1994. Identification of a novel 33-kDa C1q-binding site on human blood platelets. J. Immunol. 152:58965901.
174. Perry, V. H.,, D. A. Hume, and, S. Gordon. 1985. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15:313326.
175. Pittoni, V.,, and G. Valesini. 2002. The clearance of apoptotic cells: implications for autoimmunity. Autoimmun. Rev. 1:154161.
176. Platt, N.,, H. Suzuki,, T. Kodama, and, S. Gordon. 2000. Apoptotic thymocyte clearance in scavenger receptor class A-deficient mice is apparently normal. J. Immunol. 164:48614867.
177. Platt, N.,, H. Suzuki,, Y. Kurihara,, T. Kodama, and, S. Gordon. 1996. Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc. Natl. Acad. Sci. USA 93:1245612460.
178. Pomorski, T.,, R. Lombardi,, H. Riezman,, P. F. Devaux,, G. van Meer, and, J. C. Holthuis. 2003. Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol. Biol. Cell 14:12401254.
179. Price, B. E.,, J. Rauch,, M. A. Shia,, M. T. Walsh,, W. Lieberthal,, H. M. Gilligan,, T. O’Laughlin,, J. S. Koh, and, J. S. Levine. 1996. Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a beta 2-glycoprotein I-dependent manner. J. Immunol. 157:22012208.
180. Qu, X.,, Z. Zou,, Q. Sun,, K. Luby-Phelps,, P. Cheng,, R. N. Hogan,, C. Gilpin, and, B. Levine. 2007. Autophagy genedependent clearance of apoptotic cells during embryonic development. Cell 128:931946.
181. Reidy, M. F.,, and J. R. Wright. 2003. Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory alveolar macrophages. Am. J. Physiol. 285:L854L861.
182. Ren, Y.,, and J. Savill. 1995. Proinflammatory cytokines potentiate thrombospondin-mediated phagocytosis of neutrophils undergoing apoptosis. J. Immunol. 154:23662374.
183. Ren, Y.,, L. Stuart,, F. P. Lindberg,, A. R. Rosenkranz,, Y. Chen,, T. N. Mayadas, and, J. Savill. 2001. Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of beta 2 integrins. J. Immunol. 166:47434750.
184. Reville, K.,, J. K. Crean,, S. Vivers,, I. Dransfield, and, C. Godson. 2006. Lipoxin A4 redistributes myosin IIA and Cdc42 in macrophages: implications for phagocytosis of apoptotic leukocytes. J. Immunol. 176:18781888.
185. Roos, A.,, W. Xu,, G. Castellano,, A. J. Nauta,, P. Garred,, M. R. Daha, and, C. van Kooten. 2004. Mini-review: a pivotal role for innate immunity in the clearance of apoptotic cells. Eur. J. Immunol. 34:921929.
186. Rovere, P.,, A. A. Manfredi,, C. Vallinoto,, V. S. Zimmermann,, U. Fascio,, G. Balestrieri,, P. Ricciardi-Castagnoli,, C. Rugarli,, A. Tincani, and, M. G. Sabbadini. 1998. Dendritic cells preferentially internalize apoptotic cells opsonized by anti-beta2-glycoprotein I antibodies. J. Autoimmun. 11:403411.
187. Ryeom, S. W.,, J. R. Sparrow, and, R. L. Silverstein. 1996. CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J. Cell Sci. 109(Pt 2):387395.
188. Santiago, C.,, A. Ballesteros,, L. Martinez-Munoz,, M. Mellado,, G. G. Kaplan,, G. J. Freeman, and, J. M. Casasnovas. 2007. Structures of T cell immunoglobulin mucin protein 4 show a metal-ion-dependent ligand binding site where phosphatidylserine binds. Immunity 27:941951.
189. Santy, L. C.,, K. S. Ravichandran, and, J. E. Casanova. 2005. The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. Curr. Biol. 15:17491754.
190. Sather, S.,, K. D. Kenyon,, J. B. Lefkowitz,, X. Liang,, B. C. Varnum,, P. M. Henson, and, D. K. Graham. 2007. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood 109:10261233.
191. Savill, J.,, I. Dransfield,, C. Gregory, and, C. Haslett. 2002. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2:965975.
192. Savill, J.,, I. Dransfield,, N. Hogg, and, C. Haslett. 1990. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 343:170173.
193. Savill, J.,, C. Gregory, and, C. Haslett. 2003. Cell biology. Eat me or die. Science 302:15161517.
194. Savill, J.,, N. Hogg, and, C. Haslett. 1991. Macrophage vitronectin receptor, CD36, and thrombospondin cooperate in recognition of neutrophils undergoing programmed cell death. Chest 99:6S7S.
195. Savill, J.,, N. Hogg,, Y. Ren, and, C. Haslett. 1992. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J. Clin. Investig. 90:15131522.
196. Savill, J. S.,, P. M. Henson, and, C. Haslett. 1989. Phagocytosis of aged human neutrophils by macrophages is mediated by a novel “charge-sensitive” recognition mechanism. J. Clin. Investig. 84:15181527.
197. Scannell, M.,, M. B. Flanagan,, A. deStefani,, K. J. Wynne,, G. Cagney,, C. Godson, and, P. Maderna. 2007. Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages. J. Immunol. 178:45954605.
198. Schagat, T. L.,, J. A. Wofford, and, J. R. Wright. 2001. Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J. Immunol. 166:27272733.
199. Schulz, O.,, D. J. Pennington,, K. Hodivala-Dilke,, M. Febbraio, and, C. Reis e Sousa. 2002. CD36 or alphavbeta3 and alphavbeta5 integrins are not essential for MHC class I cross-presentation of cell-associated antigen by CD8 alpha+ murine dendritic cells. J. Immunol. 168:60576065.
200. Scott, R. S.,, E. J. McMahon,, S. M. Pop,, E. A. Reap,, R. Caricchio,, P. L. Cohen,, H. S. Earp, and, G. K. Matsushima. 2001. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207211.
201. Seitz, H. M.,, T. D. Camenisch,, G. Lemke,, H. S. Earp, and, G. K. Matsushima. 2007. Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J. Immunol. 178:56355642.
202. Sen, P.,, M. A. Wallet,, Z. Yi,, Y. Huang,, M. Henderson,, C. E. Mathews,, H. S. Earp,, G. Matsushima,, A. S. Baldwin, Jr., and, R. M. Tisch. 2007. Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood 109:653660.
203. Serhan, C. N.,, and J. Savill. 2005. Resolution of inflammation: the beginning programs the end. Nat. Immunol. 6:11911197.
204. Shiratsuchi, A.,, I. Watanabe,, O. Takeuchi,, S. Akira, and, Y. Nakanishi. 2004. Inhibitory effect of Toll-like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. J. Immunol. 172:20392047.
205. Silva, J. S.,, F. S. Machado, and, G. A. Martins. 2003. The role of nitric oxide in the pathogenesis of Chagas disease. Front. Biosci. 8:s314s325.
206. Sim, R. B.,, S. K. Moestrup,, G. R. Stuart,, N. J. Lynch,, J. Lu,, W. J. Schwaeble, and, R. Malhotra. 1998. Interaction of C1q and the collectins with the potential receptors calreticulin (cC1qR/collectin receptor) and megalin. Immunobiology 199:208224.
207. Skoberne, M.,, A. S. Beignon,, M. Larsson, and, N. Bhardwaj. 2005. Apoptotic cells at the crossroads of tolerance and immunity. Curr. Top. Microbiol. Immunol. 289:259292.
208. Skoberne, M.,, S. Somersan,, W. Almodovar,, T. Truong,, K. Petrova,, P. M. Henson, and, N. Bhardwaj. 2006. The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function. Blood 108:947955.
209. Stach, C. M.,, X. Turnay,, R. E. Voll,, P. M. Kern,, W. Kolowos,, T. D. Beyer,, J. R. Kalden, and, M. Herrmann. 2000. Treatment with annexin V increases immunogenicity of apoptotic human T-cells in Balb/c mice. Cell Death Differ. 7:911-5.
210. Stern, M.,, J. Savill, and, C. Haslett. 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. 149:911921.
211. Stuart, L. M.,, M. Lucas,, C. Simpson,, J. Lamb,, J. Savill, and, A. Lacy-Hulbert. 2002. Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation. J. Immunol. 168:16271635.
212. Stuart, L. M.,, K. Takahashi,, L. Shi,, J. Savill, and, R. A. Ezekowitz. 2005. Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J. Immunol. 174:32203226.
213. Subang, R.,, J. S. Levine,, A. S. Janoff,, S. M. Davidson,, T. F. Taraschi,, T. Koike,, S. R. Minchey,, M. Whiteside,, M. Tannenbaum, and, J. Rauch. 2000. Phospholipid-bound beta 2-glycoprotein I induces the production of anti-phospholipid antibodies. J. Autoimmun. 15:2132.
214. Subbanagounder, G.,, N. Leitinger,, D. C. Schwenke,, J. W. Wong,, H. Lee,, C. Rizza,, A. D. Watson,, K. F. Faull,, A. M. Fogelman, and, J. A. Berliner. 2000. Determinants of bio-activity of oxidized phospholipids. Specific oxidized fatty acyl groups at the sn-2 position. Arterioscler. Thromb. Vasc. Biol. 20:22482254.