Phagocytosis of apoptotic cells: A matter of balance

Cellular and Molecular Life Sciences

Volumn 62, Issue 14, 2005, Pages 1532-1546

  De Almeida, C J G ^a,b   Linden, R ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Apoptosis; Macrophage; Phagocytosis; Prion; Programmed cell death

Indexed keywords

ADENOSINE TRIPHOSPHATASE (MAGNESIUM); BETA2 GLYCOPROTEIN 1; C REACTIVE PROTEIN; CALCIUM; CALCIUM IONOPHORE; CARRIER PROTEIN; CELL RECEPTOR; CYTOSKELETON PROTEIN; GALECTIN 3; IMMUNOGLOBULIN M; INTERCELLULAR ADHESION MOLECULE 3; MANNOSE BINDING LECTIN; OPSONIN; OXIDIZED LOW DENSITY LIPOPROTEIN; PENTRAXIN; PHOSPHATIDYLSERINE; PRION PROTEIN; RECEPTOR; SERUM AMYLOID P; SURFACTANT PROTEIN A; SURFACTANT PROTEIN D; WISKOTT ALDRICH SYNDROME PROTEIN; ZYMOSAN;

ACTIN POLYMERIZATION; APOPTOSIS; CAENORHABDITIS ELEGANS; CELL ADHESION; CELL MEMBRANE; CELL TYPE; CLEARANCE; EXAMINATION; GENE EXPRESSION; GLYCOSYLATION; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; INFLAMMATION; MODULATION; MOLECULAR RECOGNITION; MUELLER CELL; NERVE CELL; NEUTROPHIL; NONHUMAN; OPSONIZATION; PERITONEUM CELL; PHAGOCYTOSIS; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; THYMOCYTE;

EID: 22544480574     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-4511-y     Document Type: Review

References (173)

1. Hedgecock E. M., Sulston J. E. and Thomson J. N. (1983) Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220: 1277-1279
2. Ellis R. E., Jacobson D. M. and Horvitz H. R. (1991) Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 129: 79-94
3. Chung S., Gumienny T. L., Hengartner M. O. and Driscoll M. (2000) A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat. Cell Biol. 2: 931-937
4. Voll R. E., Herrmann M., Roth E. A., Stach C., Kalden J. R. and Girkontaite I. (1997) Immunosuppressive effects of apoptotic cells. Nature 390: 350-351
5. Fadok V. A., Bratton D. L., Konowal A., Freed P. W., Westcott J. Y. and Henson P. M. (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. Invest. 101: 890-898
6. Lucas M., Stuart L. M., Savill J. and Lacy-Hulbert A. (2003) Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J. Immunol. 171: 2610-2615
7. Fadok V. A., Savill J. S., Haslett C., Bratton D. L., Doherty D. E., Campbell P. A. et al. (1992) Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J. Immunol. 149: 4029-4035
8. Savill J., Dransfield I., Hogg N. and Haslett C. (1990) Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 343: 170-173
9. Savill J. S., Henson P. M. and Haslett C. (1989) Phagocytosis of aged human neutrophils by macrophages is mediated by a novel 'charge-sensitive' recognition mechanism. J. Clin. Invest. 84: 1518-1527
10. Leverrier Y. and Ridley A. J. (2001) Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages. Curr. Biol. 11: 195-199
11. Taylor P. R., Carugati A., Fadok V. A., Cook H. T., Andrews M., Carroll M. C. 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
12. Scott R. S., McMahon E. J., Pop S. M., Reap E. A., Caricchio R., Cohen P. L. et al. (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411: 207-211
13. Cohen P. L., Caricchio R., Abraham V., Camenisch T. D., Jennette J. C., Roubey R. A. et al. (2002) Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J. Exp. Med. 196: 135-140
14. Pradhan D., Krahling S., Williamson P. and Schlegel R. A. (1997) Multiple systems for recognition of apoptotic lymphocytes by macrophages. Mol. Biol. Cell 8: 767-778
15. Fujii C., Shiratsuchi A., Manaka J., Yonehara S. and Nakanishi Y. (2001) Difference in the way of macrophage recognition of target cells depending on their apoptotic states. Cell Death Differ. 8: 1113-1122
16. Wiegand U. K., Corbach S., Prescott A. R., Savill J. and Spruce B. A. (2001) The trigger to cell death determines the efficiency with which dying cells are cleared by neighbours. Cell Death Differ. 8: 734-746
17. Fadok V. A., Voelker D. R., Campbell P. A., Cohen J. J., Bratton D. L. and Henson P. M. (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148: 2207-2216
18. Callahan M. K., Williamson P. and Schlegel R. A. (2000) Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes. Cell Death Differ. 7: 645-653
19. Waring P., Lambert D., Sjaarda A., Hurne A. and Beaver J. (1999) Increased cell surface exposure of phosphatidylserine on propidium iodide-negative thymocytes undergoing death by necrosis. Cell Death Differ. 6: 624-637
20. Cocco R. E. and Ucker D. S. (2001) Distinct modes of macrophage recognition for apoptotic and necrotic cells are not specified exclusively by phosphatidylserine exposure. Mol. Biol. Cell 12: 919-930
21. Dillon S. R., Mancini M., Rosen A. and Schlissel M. S. (2000) Annexin V binds to viable B cells and colocalizes with a marker of lipid rafts upon B cell receptor activation. J. Immunol. 164: 1322-1332
22. Schlegel R. A. and Williamson P. (2001) Phosphatidylserine, a death knell. Cell Death Differ. 8: 551-563
23. Freitas Balanco J. M., Moreira M. E., Bonomo A., Bozza P. T., Amarante-Mendes G., Pirmez C. et al. (2001) Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity. Curr. Biol. 11: 1870-1873
24. Luciani M. F. and Chimini G. (1996) The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death. EMBO J. 15: 226-235
25. Marguet D., Luciani M. F., Moynault A., Williamson P. and Chimini G. (1999) Engulfment of apoptotic cells involves the redistribution of membrane phosphatidylserine on phagocyte and prey. Nat. Cell Biol. 1: 454-456
26. Wu Y. C. and Horvitz H. R. (1998) The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 93: 951-960
27. Hamon Y., Chambenoit O. and Chimini G. (2002) ABCA1 and the engulfment of apoptotic cells. Biochim. Biophys. Acta 1585: 64-71
28. Williamson P. and Schlegel R. A. (2002) Transbilayer phospholipid movement and the clearance of apoptotic cells. Biochim. Biophys. Acta 1585: 53-63
29. Liu Q. A. and Hengartner M. O. (1998) Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans. Cell 93: 961-972
30. Zhou Z., Hartwieg E. and Horvitz H. R. (2001) CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104: 43-56
31. Gumienny T. L., Brugnera E., Tosello-Trampont A. C., Kinchen J. M., Haney L. B., Nishiwaki K. et al. (2001) CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107: 27-41
32. Wang X., Wu Y. C., Fadok V. A., Lee M. C., Gengyo-Ando K., Cheng L. C. et al. (2003) Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science 302: 1563-1566
33. Su H. P., Nakada-Tsukui K., Tosello-Trampont A. C., Li Y., Bu G., Henson P. M. 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
34. Arur S., Uche U. E., Rezaul K., Fong M., Scranton V., Cowan A. E. et al. (2003) Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4: 587-598
35. Fadok V. A., Bratton D. L., Rose D. M., Pearson A., Ezekewitz R. A. and Henson P. M. (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405: 85-90
36. Moffatt O. D., Devitt A., Bell E. D., Simmons D. L. and Gregory C. D. (1999) Macrophage recognition of ICAM-3 on apoptotic leukocytes. J. Immunol. 162: 6800-6810
37. Dini L., Autuori F., Lentini A., Oliverio S. and Piacentini M. (1992) The clearance of apoptotic cells in the liver is mediated by the asialoglycoprotein receptor. FEBS Lett. 296: 174-178
38. Falasca L., Bergamini A., Serafino A., Balabaud C. and Dini L. (1996) Human Kupffer cell recognition and phagocytosis of apoptotic peripheral blood lymphocytes. Exp. Cell Res. 224: 152-162
39. Azuma Y., Inami Y. and Matsumoto K. (2002) Alterations in cell surface phosphatidylserine and sugar chains during apoptosis and their time-dependent role in phagocytosis by macrophages. Biol. Pharm. Bull. 25: 1277-1281
40. Azuma Y., Taniguchi A. and Matsumoto K. (2000) Decrease in cell surface sialic acid in etoposide-treated Jurkat cells and the role of cell surface sialidase. Glycoconj. J. 17: 301-306
41. Watanabe Y., Shiratsuchi A., Shimizu K., Takizawa T. and Nakanishi Y. (2002) Role of phosphatidylserine exposure and sugar chain desialylation at the surface of influenza virus-infected cells in efficient phagocytosis by macrophages. J. Biol. Chem. 277: 18222-18228
42. Sambrano G. R. and Steinberg D. (1995) Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: role of membrane phosphatidylserine. Proc. Natl. Acad. Sci. USA 92: 1390-1400
43. Bird D. A., Gillotte K. L., Horkko S., Friedman P., Dennis E. A., Witztum J. L. et al. (1999) Receptors for oxidized low-density lipoprotein on elicited mouse peritoneal macrophages can recognize both the modified lipid moieties and the modified protein moieties: implications with respect to macrophage recognition of apoptotic cells. Proc. Natl. Acad. Sci. USA 96: 6347-6352
44. Chang M. K., Bergmark C., Laurila A., Horkko S., Han K. H., Friedman P. et al. (1999) Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition. Proc. Natl. Acad. Sci. USA 96: 6353-6358
45. Ramprasad M. P., Fischer W., Witztum J. L., Sambrano G. R., Quehenberger O. and Steinberg D. (1995) The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68. Proc. Natl. Acad. Sci. USA 92: 9580-9584
46. Platt N., Suzuki H., Kurihara Y., Kodama T. and Gordon S. (1996) Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc. Natl. Acad. Sci. USA 93: 12456-12460
47. Fukasawa M., Adachi H., Hirota K., Tsujimoto M., Arai H. and Inoue K. (1996) SRB1, a class B scavenger receptor, recognizes both negatively charged liposomes and apoptotic cells. Exp. Cell Res. 222: 246-250
48. Oka K., Sawamura T., Kikuta K., Itokawa S., Kume N., Kita T. et al. (1998) Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells. Proc. Natl. Acad. Sci. USA 95: 9535-9540
49. Kagan V. E., Gleiss B., Tyurina Y. Y., Tyurin V. A., Elenstrom-Magnusson C., Liu S. X. 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
50. Matsura T., Serinkan B. F., Jiang J. and Kagan V. E. (2002) Phosphatidylserine peroxidation/externalization during staurosporine-induced apoptosis in HL-60 cells. FEBS Lett. 524: 25-30
51. Matsui H., Tsuji S., Nishimura H. and Nagasawa S. (1994) Activation of the alternative pathway of complement by apoptotic Jurkat cells. FEBS Lett. 351: 419-422
52. Tsuji S., Kaji K. and Nagasawa S. (1994) Activation of the alternative pathway of human complement by apoptotic human umbilical vein endothelial cells. J. Biochem. (Tokyo) 116: 794-800
53. Takizawa F., Tsuji S. and Nagasawa S. (1996) Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett. 397: 269-272
54. Mold C. and Morris C. A. (2001) Complement activation by apoptotic endothelial cells following hypoxia/reoxygenation. Immunology 102: 359-364
55. Mevorach D., Mascarenhas J. O., Gershov D. and Elkon K. B. (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J. Exp. Med. 188: 2313-2320
56. Gaipl U. S., Kuenkele S., Voll R. E., Beyer T. D., Kolowos W., Heyder P. et al. (2001) Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ. 8: 327-334
57. Ogden C. A., deCathelineau A., Hoffmann P. R., Bratton D., Ghebrehiwet B., Fadok V. A. 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
58. Nauta A. J., Castellano G., Xu W., Woltman A. M., Borrias M. C., Daha M. R. et al. (2004) Opsonization with C1q and mannose-binding lectin targets apoptotic cells to dendritic cells. J. Immunol. 173: 3044-3050
59. Botto M., Dell'Agnola C., Bygrave A. E., Thompson E. M., Cook H. T., Petry F. et al. (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19: 56-59
60. Kim S. J., Gershov D., Ma X., Brot N. and Elkon K. B. (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: 655-665
61. Chonn A., Semple S. C. and Cullis P. R. (1995) Beta 2 glycoprotein I is a major protein associated with very rapidly cleared liposomes in vivo, suggesting a significant role in the immune clearance of 'non-self' particles. J. Biol. Chem. 270: 25845-25849
62. Balasubramanian K., Chandra J. and Schroit A. J. (1997) Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. J. Biol. Chem. 272: 31113-31117
63. Rovere P., Manfredi A. A., Vallinoto C., Zimmermann V. S., Fascio U., Balestrieri G. et al. (1998) Dendritic cells preferentially internalize apoptotic cells opsonized by anti-beta2-glycoprotein I antibodies. J. Autoimmun. 11: 403-411
64. Nauta A. J., Raaschou-Jensen N., Roos A., Daha M. R., Madsen H. O., Borrias-Essers M. C. et al. (2003) Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur. J. Immunol. 33: 2853-2863
65. Schagat T. L., Wofford J. A. and Wright J. R. (2001) Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J. Immunol. 166: 2727-2733
66. Vandivier R. W., Ogden C. A., Fadok V. A., Hoffmann P. R., Brown K. K., Botto M. et al. (2002) 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. 169: 3978-3986
67. Gershov D., Kim S., Brot N. and Elkon K. B. (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: 1353-1364
68. Mold C., Baca R. and Du Clos T. W. (2002) Serum amyloid P component and C-reactive protein opsonize apoptotic cells for phagocytosis through Fcgamma receptors. J. Autoimmun. 19: 147-154
69. Bijl M., Horst G., Bijzet J., Bootsma H., Limburg P. C. and Kallenberg C. G. (2003) Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte-derived macrophages. Arthritis Rheum. 48: 248-254
70. Anderson H. A., Maylock C. A., Williams J. A., Paweletz C. P., Shu H. and Shacter E. (2003) Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat. Immunol. 4: 87-91
71. Henson P. M., Bratton D. L. and Fadok V. A. (2001) The phosphatidylserine receptor: a crucial molecular switch? Nat. Rev. Mol. Cell Biol. 2: 627-633
72. Hoffmann P. R., deCathelineau A. M., Ogden C. A., Leverrier Y., Bratton D. L., Daleke D. L. et al. (2001) Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J. Cell Biol. 155: 649-659
73. Li M. O., Sarkisian M. R., Mehal W. Z., Rakic P. and Flavell R. A. (2003) Phosphatidylserine receptor is required for clearance of apoptotic cells. Science 302: 1560-1563
74. Bose J., Gruber A. D., Helming L., Schiebe S., Wegener I., Hafner M. et al. (2004) The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. J. Biol. 3: 15
75. Kunisaki Y., Masuko S., Noda M., Inayoshi A., Sanui T., Harada M. et al. (2004) Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor. Blood 103: 3362-3364
76. Shiratsuchi A., Kawasaki Y., Ikemoto M., Arai H. and Nakanishi Y. (1999) Role of class B scavenger receptor type I in phagocytosis of apoptotic rat spermatogenic cells by Sertoli cells. J. Biol. Chem. 274: 5901-5908
77. Tait J. F. and Smith C. (1999) Phosphatidylserine receptors: role of CD36 in binding of anionic phospholipid vesicles to monocytic cells. J. Biol. Chem. 274: 3048-3054
78. Devitt A., Moffatt O. D., Raykundalia C., Capra J. D., Simmons D. L. and Gregory C. D. (1998) Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392: 505-509
79. Devitt A., Pierce S., Oldreive C., Shingler W. H. and Gregory C. D. (2003) CD14-dependent clearance of apoptotic cells by human macrophages: the role of phosphatidylserine. Cell Death Differ. 10: 371-382
80. Fan X., Krahling S., Smith D., Williamson P. and Schlegel R. A. (2004) Macrophage surface expression of annexins I and II in the phagocytosis of apoptotic lymphocytes. Mol. Biol. Cell 15: 2863-2872
81. Nakano T., Ishimoto Y., Kishino J., Umeda M., Inoue K., Nagata K. et al. (1997) Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. J. Biol. Chem. 272: 29411-29414
82. Ishimoto Y., Ohashi K., Mizuno K. and Nakano T. (2000) Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J. Biochem. (Tokyo) 127: 411-417
83. Gregory C. D. (2000) CD14-dependent clearance of apoptotic cells: relevance to the immune system. Curr. Opin. Immunol. 12: 27-34
84. Schlegel R. A., Krahling S., Callahan M. K. and Williamson P. (1999) CD14 is a component of multiple recognition systems used by macrophages to phagocytose apoptotic lymphocytes. Cell Death Differ. 6: 583-592
85. Duvall E., Wyllie A. H. and Morris R. G. (1985) Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology 56: 351-358
86. Hall S. E., Savill J. S., Henson P. M. and Haslett C. (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: 3218-3227
87. Norsworthy P. J., Fossati-Jimack L., Cortes-Hernandez J., Taylor P. R., Bygrave A. E., Thompson R. D. 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
88. Schwartz B. R., Karsan A., Bombeli T. and Harlan J. M. (1999) A novel beta 1 integrin-dependent mechanism of leukocyte adherence to apoptotic cells. J. Immunol. 162: 4842-4848
89. Blystone S. D., Graham I. L., Lindberg F. P. and Brown E. J. (1994) Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1. J. Cell Biol. 127: 1129-1137
90. Blystone S. D., Lindberg F. P., LaFlamme S. E. and Brown E. J. (1995) Integrin beta 3 cytoplasmic tail is necessary and sufficient for regulation of alpha 5 beta 1 phagocytosis by alpha v beta 3 and integrin-associated protein. J. Cell Biol. 130: 745-754
91. McCutcheon J. C., Hart S. P., Canning M., Ross K., Humphries M. J. and Dransfield I. (1998) Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin. J. Leukoc. Biol. 64: 600-607
92. Hart S. P., Dougherty G. J., Haslett C. and Dransfield I. (1997) CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages. J. Immunol. 159: 919-925
93. Johnson J. D., Hess K. L. and Cook-Mills J. M. (2003) CD44, alpha(4) integrin, and fucoidin receptor-mediated phagocytosis of apoptotic leukocytes. J. Leukoc. Biol. 74: 810-820
94. Teder P., Vandivier R. W., Jiang D., Liang J., Cohn L., Pure E. et al. (2002) Resolution of lung inflammation by CD44. Science 296: 155-158
95. Hanayama R., Tanaka M., Miwa K., Shinohara A., Iwamatsu A. and Nagata S. (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417: 182-187
96. Hanayama R., Tanaka M., Miwa K. and Nagata S. (2004) Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J. Immunol. 172: 3876-3882
97. Hanayama R., Tanaka M., Miyasaka K., Aozasa K., Koike M., Uchiyama Y. et al. (2004) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304: 1147-1150
98. high polymorphonuclear neutrophils in the murine abdominal cavity. Clin. Diagn. Lab Immunol. 11: 452-457
99. Akakura S., Singh S., Spataro M., Akakura R., Kim J. I., Albert M. L. et al. (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: 403-416
100. Wu Y., Singh S., Georgescu M. M. and Birge R. B. (2005) A role for Mer tyrosine kinase in {alpha}v{beta}5 integrin-mediated phagocytosis of apoptotic cells. J. Cell Sci. 118: 539-553
101. Krahling S., Callahan M. K., Williamson P. and Schlegel R. A. (1999) Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages. Cell Death Differ. 6: 183-189
102. Albert M. L., Pearce S. F., Francisco L. M., Sauter B., Roy P., Silverstein R. L. et al. (1998) Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188: 1359-1368
103. Finnemann S. C. and Rodriguez-Boulan E. (1999) Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage. J. Exp. Med. 190: 861-874
104. Finnemann S. C., Bonilha V. L., Marmorstein A. D. and Rodriguez-Boulan E. (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: 12932-12937
105. Lin H. and Clegg D. O. (1998) Integrin alphavbeta5 participates in the binding of photoreceptor rod outer segments during phagocytosis by cultured human retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 39: 1703-1712
106. Finnemann S. C. and Silverstein R. L. (2001) Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J. Exp. Med. 194: 1289-1298
107. Ryeom S. W., Sparrow J. R. and Silverstein R. L. (1996) CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J. Cell Sci. 109 (Pt 2): 387-395
108. Miceli M. V., Newsome D. A. and Tate D. J., Jr. (1997) Vitronectin is responsible for serum-stimulated uptake of rod outer segments by cultured retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 38: 1588-1597
109. Boyle D., Tien L. F., Cooper N. G., Shepherd V. and McLaughlin B. J. (1991) A mannose receptor is involved in retinal phagocytosis. Invest. Ophthalmol. Vis. Sci. 32: 1464-1470
110. Lutz D. A., Guo Y. and McLaughlin B. J. (1995) Natural, high-mannose glycoproteins inhibit ROS binding and ingestion by RPE cell cultures. Exp. Eye Res. 61: 487-493
111. Yamanaka M., Eda S. and Beppu M. (2005) Carbohydrate chains and phosphatidylserine successively work as signals for apoptotic cell removal. Biochem. Biophys. Res. Commun. 328: 273-280
112. Adayev T., Estephan R., Meserole S., Mazza B., Yurkow E. J. and Banerjee P. (1998) Externalization of phosphatidylserine may not be an early signal of apoptosis in neuronal cells, but only the phosphatidylserine-displaying apoptotic cells are phagocytosed by microglia. J. Neurochem. 71: 1854-1864
113. Weiss D. J., Evanson O. A., Deng M. and Abrahamsen M. S. (2004) Sequential patterns of gene expression by bovine monocyte-derived macrophages associated with ingestion of mycobacterial organisms. Microb. Pathog. 37: 215-224
114. Sano H., Hsu D. K., Apgar J. R., Yu L., Sharma B. B., Kuwabara I. et al. (2003) Critical role of galectin-3 in phagocytosis by macrophages. J. Clin. Invest. 112: 389-397
115. Albert M. L., Kim J. I. and Birge R. B. (2000) alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells. Nat. Cell Biol. 2: 899-905
116. Reddien P. W. and Horvitz H. R. (2000) CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat. Cell Biol. 2: 131-136
117. Wu Y. C., Tsai M. C., Cheng L. C., Chou C. J. and Weng N. Y. (2001) C. elegans CED-12 acts in the conserved crkII/ DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Dev. Cell 1: 491-502
118. deBakker C. D., Haney L. B., Kinchen J. M., Grimsley C., Lu M., Klingele D. et al. (2004) Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Curr. Biol. 14: 2208-2216
119. Tosello-Trampont A. C., Brugnera E. and Ravichandran K. S. (2001) Evidence for a conserved role for CRKII and Rac in engulfment of apoptotic cells. J. Biol. Chem. 276: 13797-13802
120. Mahajan N. P. and Earp H. S. (2003) An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J. Biol. Chem. 278: 42596-42603
121. Giles K. M., Ross K., Rossi A. G., Hotchin N. A., Haslett C. and Dransfield I. (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: 976-986
122. Liu Y., Cousin J. M., Hughes J., Van Damme J., Seckl J. R., Haslett C. et al. (1999) Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J. Immunol. 162: 3639-3646
123. Chimini G. and Chavrier P. (2000) Function of Rho family proteins in actin dynamics during phagocytosis and engulfment. Nat. Cell Biol. 2: E191-E196
124. Takenawa T. and Miki H. (2001) WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci. 114: 1801-1809
125. Leverrier Y., Lorenzi R., Blundell M. P., Brickell P., Kinnon C., Ridley A. J. et al. (2001) Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells. J. Biol. Chem. 166: 4831-4834
126. Miller Y. I., Chang M. K., Funk C. D., Feramisco J. R. and Witztum J. L. (2001) 12/15-lipoxygenase translocation enhances site-specific actin polymerization in macrophages phagocytosing apoptotic cells. J. Biol. Chem. 276: 19431-19439
127. Hu B., Punturieri A., Todt J., Sonstein J., Polak T. and Curtis J. L. (2002) Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events. J. Leukoc. Biol. 71: 881-889
128. Leverrier Y., Okkenhaug K., Sawyer C., Bilancio A., Vanhaesebroeck B. and Ridley A. J. (2003) Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages. J. Biol. Chem. 278: 38437-38442
129. Todt J. C., Hu B., Punturieri A., Sonstein J., Polak T. and Curtis J. L. (2002) Activation of protein kinase C beta II by the stereo-specific phosphatidylserine receptor is required for phagocytosis of apoptotic thymocytes by resident murine tissue macrophages. J. Biol. Chem. 277: 35906-35914
130. Babior B. M. (2000) Phagocytes and oxidative stress. Am. J. Med. 109: 33-44
131. Gresham H. D., Dale B. M., Potter J. W., Chang P. W., Vines C. M., Lowell C. A. et al. (2000) Negative regulation of phagocytosis in murine macrophages by the Src kinase family member, Fgr. J. Exp. Med. 191: 515-528
132. Hu B., Sonstein J., Christensen P. J., Punturieri A. and Curtis J. L. (2000) Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident murine alveolar macrophages. J. Immunol. 165: 2124-2133
133. Jennings J. H., Linderman D. J., Hu B., Sonstein J. and Curtis J. L. (2005) Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly. Am. J. Respir. Cell Mol. Biol. 32: 108-117
134. Freire-de-Lima C. G., Nascimento D. O., Soares M. B., Bozza P. T., Castro-Faria-Neto H. C., de Mello F. G. et al. (2000) Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature 403: 199-203
135. Lopes M. F., Freire-de-Lima C. G. and DosReis G. A. (2000) The macrophage haunted by cell ghosts: a pathogen grows. Immunol. Today 21: 489-494
136. Vivier E. and Daeron M. (1997) Immunoreceptor tyrosine-based inhibition motifs. Immunol. Today 18: 286-291
137. D'Ambrosio D., Fong D. C. and Cambier J. C. (1996) The SHIP phosphatase becomes associated with Fc gammaRIIB1 and is tyrosine phosphorylated during 'negative' signaling. Immunol. Lett. 54: 77-82
138. Sarmay G., Koncz G., Pecht I. and Gergely J. (1997) Fc gamma receptor type IIb induced recruitment of inositol and protein phosphatases to the signal transductory complex of human B-cell. Immunol. Lett. 57: 159-164
139. Vogel W., Lammers R., Huang J. and Ullrich A. (1993) Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science 259: 1611-1614
140. Brown S., Heinisch I., Ross E., Shaw K., Buckley C. D. and Savill J. (2002) Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 418: 200-203
141. Medzhitov R. and Janeway C. A., Jr. (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296: 298-300
142. Oldenborg P. A., Zheleznyak A., Fang Y. F., Lagenaur C. F., Gresham H. D. and Lindberg F. P. (2000) Role of CD47 as a marker of self on red blood cells. Science 288: 2051-2054
143. Oldenborg P. A., Gresham H. D. and Lindberg F. P. (2001) CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis. Science 193: 855-862
144. Yamao T., Noguchi T., Takeuchi O., Nishiyama U., Morita H., Hagiwara T. et al. (2002) Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J. Biol. Chem. 277: 39833-39839
145. Tada K., Tanaka M., Hanayama R., Miwa K., Shinohara A., Iwamatsu A. et al. (2003) Tethering of apoptotic cells to phagocytes through binding of CD47 to Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1. J. Immunol. 171: 5718-5726
146. Erwig L. P., Gordon S., Walsh G. M. and Rees A. J. (1999) Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils. Blood 93: 1406-1412
147. Broderick C., Hoek R. M., Forrester J. V., Liversidge J., Sedgwick J. D. and Dick A. D. (2002) Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. Am. J. Pathol. 161: 1669-1677
148. Dick A. D., Carter D., Robertson M., Broderick C., Hughes E., Forrester J. V. et al. (2003) Control of myeloid activity during retinal inflammation. J. Leukoc. Biol. 74: 161-166
149. Hoek R. M., Ruuls S. R., Murphy C. A., Wright G. J., Goddard R., Zurawski S. M. et al. (2000) Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290: 1768-1771
150. Tosello-Trampont A. C., Nakada-Tsukui K. and Ravichandran K. S. (2003) Engulfment of apoptotic cells is negatively regulated by Rho-mediated signaling. J. Biol. Chem. 278: 49911-49919
151. Rossi A. G., McCutcheon J. C., Roy N., Chilvers E. R., Haslett C. and Dransfield I. (1998) Regulation of macrophage phagocytosis of apoptotic cells by cAMP. J. Immunol. 160: 3562-3568
152. Godson C., Mitchell S., Harvey K., Petasis N. A., Hogg N. and Brady H. R. (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J. Immunol. 164: 1663-1667
153. Rovere P., Peri G., Fazzini F., Bottazzi B., Doni A., Bondanza A. et al. (2000) The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 96: 4300-4306
154. van Rossum A. P., Fazzini F., Limburg P. C., Manfredi A. A., Rovere-Querini P., Mantovani A. et al. (2004) The prototypic tissue pentraxin PTX3, in contrast to the short pentraxin serum amyloid P, inhibits phagocytosis of late apoptotic neutrophils by macrophages. Arthritis Rheum. 50: 2667-2674
155. Kask L., Trouw L. A., Dahlback B. and Blom A. M. (2004) The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells. J. Biol. Chem. 279: 23869-23873
156. de Almeida C. J., Chiarini L. B., da Silva J. P., Silva P. M., Martins M. A. and Linden R. (2005) The cellular prion protein modulates phagocytosis and inflammatory response. J. Leukoc. Biol. 77: 238-246
157. Chimini G. (2001) Engulfing by lipids: a matter of taste? Cell Death Differ. 8: 545-548
158. Peyron P., Bordier C., N'Diaye E. N. and Maridonneau-Parini I. (2000) Nonopsonic phagocytosis of Mycobacterium kansasii by human neutrophils depends on cholesterol and is mediated by CR3 associated with glycosylphosphatidylinositol-anchored proteins. J. Immunol. 165: 5186-5191
159. Perry V. H., Bell M. D., Brown H. C. and Matyszak M. K. (1995) Inflammation in the nervous system. Curr. Opin. Neurobiol. 5: 636-641
160. Brown D. R., Besinger A., Herms J. W. and Kretzschmar H. A. (1998) Microglial expression of the prion protein. Neuroreport 9: 1425-1429
161. Brown D. R., Schmidt B. and Kretzschmar H. A. (1996) Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature 380: 345-347
162. Becquet F., Goureau O., Soubrane G., Coscas G., Courtois Y. and Hicks D. (1994) Superoxide inhibits proliferation and phagocytic internalization of photoreceptor outer segments by bovine retinal pigment epithelium in vitro. Exp. Cell Res. 212: 374-382
163. Crowell R. E., Hallin G., Heaphy E. and Mold C. (1995) Hyperoxic suppression of Fc-gamma receptor-mediated phagocytosis by isolated murine pulmonary macrophages. Am. J. Respir. Cell Mol. Biol. 12: 190-195
164. Forman H. J. and Skelton D. C. (1990) Protection of alveolar macrophages from hyperoxia by gamma-glutamyl transpeptidase. Am. J. Physiol. 259: L102-L107
165. Murphy J. K., Hoyal C. R., Livingston F. R. and Forman H. J. (1995) Modulation of the alveolar macrophage respiratory burst by hydroperoxides. Free Radic. Biol. Med. 18: 37-45
166. Oosting R. S., van Bree L., van Iwaarden J. F., van Golde L. M. and Verhoef J. (1990) Impairment of phagocytic functions of alveolar macrophages by hydrogen peroxide. Am. J. Physiol. 259: L87-L94
167. Takeda H., Tomita M., Tanahashi N., Kobari M., Yokoyama M., Takao M. et al. (1998) Hydrogen peroxide enhances phagocytic activity of ameboid microglia. Neurosci. Lett. 240: 5-8
168. Becquet F., Courtois Y. and Goureau O. (1994) Nitric oxide decreases in vitro phagocytosis of photoreceptor outer segments by bovine retinal pigmented epithelial cells. J. Cell Physiol. 159: 256-262
169. Jun C. D., Han M. K., Kim U. H. and Chung H. T. (1996) Nitric oxide induces ADP-ribosylation of actin in murine macrophages: association with the inhibition of pseudopodia formation, phagocytic activity, and adherence on a laminin substratum. Cell Immunol. 174: 25-34
170. Kopec K. K. and Carroll R. T. (2000) Phagocytosis is regulated by nitric oxide in murine microglia. Nitric Oxide 4: 103-111
171. Su S. H., Chen H. and Jen C. J. (2001) C57BL/6 and BALB/c bronchoalveolar macrophages respond differently to exercise. J. Immunol. 167: 5084-5091
172. Elward K. and Gasque P. (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: 85-94
173. Ciesielski-Treska J., Grant N. J., Ulrich G., Corrotte M., Bailly Y., Haeberle A. M. et al. (2004) Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia. Glia 46: 101-115