The immune functions of phosphatidylserine in membranes of dying cells and microvesicles

Seminars in Immunopathology

Volumn 33, Issue 5, 2011, Pages 497-516

  Frey, Benjamin ^a   Gaipl, Udo S ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Annexin A5; Apoptosis; Cancer; Clearance; Microvesicles; Phosphatidylserine

Indexed keywords

PHOSPHATIDYLSERINE;

ANIMAL; AUTOIMMUNE DISEASE; CELL DEATH; CELL MEMBRANE; CHEMISTRY; HUMAN; IMMUNOLOGY; INFLAMMATION; MEMBRANE MICROPARTICLE; METABOLISM; NEOPLASM; PHYSIOLOGY; REVIEW;

ANIMALS; AUTOIMMUNE DISEASES; CELL DEATH; CELL MEMBRANE; CELL-DERIVED MICROPARTICLES; HUMANS; INFLAMMATION; NEOPLASMS; PHOSPHATIDYLSERINES;

EID: 85027933609     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-010-0228-6     Document Type: Review

References (181)

1. Andersen MH, Graversen H, Fedosov SN, Petersen TE, Rasmussen JT (2000) Functional analyses of two cellular binding domains of bovine lactadherin. Biochemistry 39:6200–6206 DOI: 10.1021/bi992221r
2. Anderson HA, Maylock CA, Williams JA, Paweletz CP, Shu H, Shacter E (2003) Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol 4:87–91 DOI: 10.1038/ni871
3. Antwi-Baffour S, Kholia S, Aryee YK, Ansa-Addo EA, Stratton D, Lange S, Inal JM (2010) Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells—possible role in SLE. Biochem Biophys Res Commun 398:278–283 DOI: 10.1016/j.bbrc.2010.06.079
4. Apetoh L, Ghiringhelli F, Tesniere A, Criollo A, Ortiz C, Lidereau R, Mariette C, Chaput N, Mira JP, Delaloge S, Andre F, Tursz T, Kroemer G, Zitvogel L (2007) The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev 220:47–59 DOI: 10.1111/j.1600-065X.2007.00573.x
5. Appelt U, Sheriff A, Gaipl US, Kalden JR, Voll RE, Herrmann M (2005) Viable, apoptotic and necrotic monocytes expose phosphatidylserine: cooperative binding of the ligand annexin V to dying but not viable cells and implications for PS-dependent clearance. Cell Death Differ 12:194–196 DOI: 10.1038/sj.cdd.4401527
6. Ardoin SP, Shanahan JC, Pisetsky DS (2007) The role of microparticles in inflammation and thrombosis. Scand J Immunol 66:159–165 DOI: 10.1111/j.1365-3083.2007.01984.x
7. Arur S, Uche UE, Rezaul K, Fong M, Scranton V, Cowan AE, Mohler W, Han DK (2003) Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev Cell 4:587–598 DOI: 10.1016/S1534-5807(03)00090-X
8. Asano K, Miwa M, Miwa K, Hanayama R, Nagase H, Nagata S, Tanaka M (2004) Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice. J Exp Med 200:459–467 DOI: 10.1084/jem.20040342
9. Aymeric L, Apetoh L, Ghiringhelli F, Tesniere A, Martins I, Kroemer G, Smyth MJ, Zitvogel L (2010) Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 70:855–858 DOI: 10.1158/0008-5472.CAN-09-3566
10. Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Zembala M (2007) Tumour-derived microvesicles modulate biological activity of human monocytes. Immunol Lett 113:76–82 DOI: 10.1016/j.imlet.2007.07.014
11. Balasubramanian K, Chandra J, Schroit AJ (1997) Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of beta2-glycoprotein I in macrophage recognition. J Biol Chem 272:31113–31117 DOI: 10.1074/jbc.272.49.31113
12. Balasubramanian K, Schroit AJ (2003) Aminophospholipid asymmetry: a matter of life and death. Annu Rev Physiol 65:701–734 DOI: 10.1146/annurev.physiol.65.092101.142459
13. Berghe TV, Vanlangenakker N, Parthoens E, Deckers W, Devos M, Festjens N, Guerin CJ, Brunk UT, Declercq W, Vandenabeele P (2010) Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ 17:922–930 DOI: 10.1038/cdd.2009.184
14. Bles N, Di Pietrantonio L, Boeynaems JM, Communi D (2010) ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion. Blood. doi: 10.1182/blood-2010-01-265611
15. Boddaert J, Kinugawa K, Lambert JC, Boukhtouche F, Zoll J, Merval R, Blanc-Brude O, Mann D, Berr C, Vilar J, Garabedian B, Journiac N, Charue D, Silvestre JS, Duyckaerts C, Amouyel P, Mariani J, Tedgui A, Mallat Z (2007) Evidence of a role for lactadherin in Alzheimer’s disease. Am J Pathol 170:921–929 DOI: 10.2353/ajpath.2007.060664
16. Bondanza A, Zimmermann VS, Rovere-Querini P, Turnay J, Dumitriu IE, Stach CM, Voll RE, Gaipl US, Bertling W, Poschl E, Kalden JR, Manfredi AA, Herrmann M (2004) Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J Exp Med 200:1157–1165 DOI: 10.1084/jem.20040327
17. Borisenko GG, Iverson SL, Ahlberg S, Kagan VE, Fadeel B (2004) Milk fat globule epidermal growth factor 8 (MFG-E8) binds to oxidized phosphatidylserine: implications for macrophage clearance of apoptotic cells. Cell Death Differ 11:943–945 DOI: 10.1038/sj.cdd.4401421
18. Bose J, Gruber AD, Helming L, Schiebe S, Wegener I, Hafner M, Beales M, Kontgen F, Lengeling A (2004) The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. J Biol 3:15 DOI: 10.1186/jbiol10
19. Bottcher A, Gaipl US, Furnrohr BG, Herrmann M, Girkontaite I, Kalden JR, Voll RE (2006) Involvement of phosphatidylserine, alphavbeta3, CD14, CD36, and complement C1q in the phagocytosis of primary necrotic lymphocytes by macrophages. Arthritis Rheum 54:927–938 DOI: 10.1002/art.21660
20. Bratton DL, Henson PM (2008) Apoptotic cell recognition: will the real phosphatidylserine receptor(s) please stand up? Curr Biol 18:R76–R79 DOI: 10.1016/j.cub.2007.11.024
21. Bretscher MS, Raff MC (1975) Mammalian plasma membranes. Nature 258:43–49 DOI: 10.1038/258043a0
22. Burvenich I, Schoonooghe S, Vervoort L, Dumolyn C, Coene E, Vanwalleghem L, Van Huysse J, Praet M, Cuvelier C, Mertens N, De Vos F, Slegers G (2008) Monoclonal antibody 14C5 targets integrin alphavbeta5. Mol Cancer Ther 7:3771–3779 DOI: 10.1158/1535-7163.MCT-08-0600
23. Callahan MK, Halleck MS, Krahling S, Henderson AJ, Williamson P, Schlegel RA (2003) Phosphatidylserine expression and phagocytosis of apoptotic thymocytes during differentiation of monocytic cells. J Leukoc Biol 74:846–856 DOI: 10.1189/jlb.0902433
24. Callahan MK, Popernack PM, Tsutsui S, Truong L, Schlegel RA, Henderson AJ (2003) Phosphatidylserine on HIV envelope is a cofactor for infection of monocytic cells. J Immunol 170:4840–4845
25. Camenisch TD, Koller BH, Earp HS, Matsushima GK (1999) A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock. J Immunol 162:3498–3503
26. Casciola-Rosen L, Rosen A, Petri M, Schlissel M (1996) Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc Natl Acad Sci USA 93:1624–1629 DOI: 10.1073/pnas.93.4.1624
27. Chaurio RA, Janko C, Munoz LE, Frey B, Herrmann M, Gaipl US (2009) Phospholipids: key players in apoptosis and immune regulation. Molecules 14:4892–4914 DOI: 10.3390/molecules14124892
28. Chen C, Skog J, Hsu CH, Lessard RT, Balaj L, Wurdinger T, Carter BS, Breakefield XO, Toner M, Irimia D (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10:505–511 DOI: 10.1039/b916199f
29. Choi DS, Lee JM, Park GW, Lim HW, Bang JY, Kim YK, Kwon KH, Kwon HJ, Kim KP, Gho YS (2007) Proteomic analysis of microvesicles derived from human colorectal cancer cells. J Proteome Res 6:4646–4655 DOI: 10.1021/pr070192y
30. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51 DOI: 10.1016/j.tcb.2008.11.003
31. Cullis PR, Fenske DB, Hope MJ (1996) Physical properties and functional roles of lipids in membranes. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier Science, New York, pp 1–32 DOI: 10.1016/S0167-7306(08)60508-6
32. DeKruyff RH, Bu X, Ballesteros A, Santiago C, Chim YL, Lee HH, Karisola P, Pichavant M, Kaplan GG, Umetsu DT, Freeman GJ, Casasnovas JM (2010) T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells. J Immunol 184:1918–1930 DOI: 10.4049/jimmunol.0903059
33. Devaux PF (1991) Static and dynamic lipid asymmetry in cell membranes. Biochemistry 30:1163–1173 DOI: 10.1021/bi00219a001
34. Dillon SR, Mancini M, Rosen A, Schlissel MS (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
35. Distler JH, Pisetsky DS, Huber LC, Kalden JR, Gay S, Distler O (2005) Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases. Arthritis Rheum 52:3337–3348 DOI: 10.1002/art.21350
36. Dowhan W, Bogdanov M, Mileykovskaya E (2008) Functional roles of lipids in membranes. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier, Amsterdam, pp 1–38 DOI: 10.1016/B978-044453219-0.50003-9
37. Dowhan W, Bogdanov M, Mileykovskaya E (2008) Functional roles of lipids in membranes. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier, New York, pp 2–36
38. Dumitriu IE, Roedel F, Beyer TD, Gaipl US, Kalden JR, Herrmann M (2003) UV or X-irradiation increases the cytoplasmic accumulation of rhodamine 123 in various cancer cell lines. Strahlenther Onkol 179:564–570 DOI: 10.1007/s00066-003-1079-z
39. Eken C, Gasser O, Zenhaeusern G, Oehri I, Hess C, Schifferli JA (2008) Polymorphonuclear neutrophil-derived ectosomes interfere with the maturation of monocyte-derived dendritic cells. J Immunol 180:817–824
40. Elliott JI, Surprenant A, Marelli-Berg FM, Cooper JC, Cassady-Cain RL, Wooding C, Linton K, Alexander DR, Higgins CF (2005) Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes. Nat Cell Biol 7:808–816 DOI: 10.1038/ncb1279
41. Elliott JI, Sardini A, Cooper JC, Alexander DR, Davanture S, Chimini G, Higgins CF (2006) Phosphatidylserine exposure in B lymphocytes: a role for lipid packing. Blood 108:1611–1617 DOI: 10.1182/blood-2005-11-012328
42. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286 DOI: 10.1038/nature08296
43. Elliott MR, Ravichandran KS (2010) Clearance of apoptotic cells: implications in health and disease. J Cell Biol 189:1059–1070 DOI: 10.1083/jcb.201004096
44. Emoto K, Toyama-Sorimachi N, Karasuyama H, Inoue K, Umeda M (1997) Exposure of phosphatidylethanolamine on the surface of apoptotic cells. Exp Cell Res 232:430–434 DOI: 10.1006/excr.1997.3521
45. Fadeel B (2004) Plasma membrane alterations during apoptosis: role in corpse clearance. Antioxid Redox Signal 6:269–275 DOI: 10.1089/152308604322899332
46. Fadeel B, Xue D (2006) PS externalization: from corpse clearance to drug delivery. Cell Death Differ 13:360–362 DOI: 10.1038/sj.cdd.4401836
47. Fadeel B, Xue D (2009) The ins and outs of phospholipid asymmetry in the plasma membrane: roles in health and disease. Crit Rev Biochem Mol Biol 44:264–277 DOI: 10.1080/10409230903193307
48. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216
49. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90 DOI: 10.1038/35011084
50. Falkowski M, Schledzewski K, Hansen B, Goerdt S (2003) Expression of stabilin-2, a novel fasciclin-like hyaluronan receptor protein, in murine sinusoidal endothelia, avascular tissues, and at solid/liquid interfaces. Histochem Cell Biol 120:361–369 DOI: 10.1007/s00418-003-0585-5
51. Fischer N, Haug M, Kwok WW, Kalbacher H, Wernet D, Dannecker GE, Holzer U (2010) Involvement of CD91 and scavenger receptors in Hsp70-facilitated activation of human antigen-specific CD4+ memory T cells. Eur J Immunol 40:986–997 DOI: 10.1002/eji.200939738
52. Foell D, Wittkowski H, Roth J (2007) Mechanisms of disease: a ‘DAMP’ view of inflammatory arthritis. Nat Clin Pract Rheumatol 3:382–390 DOI: 10.1038/ncprheum0531
53. Fourcade O, Simon MF, Viode C, Rugani N, Leballe F, Ragab A, Fournie B, Sarda L, Chap H (1995) Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80:919–927 DOI: 10.1016/0092-8674(95)90295-3
54. Franz S, Frey B, Sheriff A, Gaipl US, Beer A, Voll RE, Kalden JR, Herrmann M (2006) Lectins detect changes of the glycosylation status of plasma membrane constituents during late apoptosis. Cytom A 69:230–239 DOI: 10.1002/cyto.a.20206
55. Franz S, Gaipl US, Munoz LE, Sheriff A, Beer A, Kalden JR, Herrmann M (2006) Apoptosis and autoimmunity: when apoptotic cells break their silence. Curr Rheumatol Rep 8:245–247 DOI: 10.1007/s11926-006-0001-y
56. Franz S, Herrmann K, Furnrohr BG, Sheriff A, Frey B, Gaipl US, Voll RE, Kalden JR, Jack HM, Herrmann M (2007) After shrinkage apoptotic cells expose internal membrane-derived epitopes on their plasma membranes. Cell Death Differ 14:733–742 DOI: 10.1038/sj.cdd.4402066
57. Frey B, Schildkopf P, Rodel F, Weiss EM, Munoz LE, Herrmann M, Fietkau R, Gaipl US (2009) AnnexinA5 renders dead tumor cells immunogenic—implications for multimodal cancer therapies. J Immunotoxicol 6:209–216 DOI: 10.3109/15476910903204058
58. Gaipl US, Kuenkele S, Voll RE, Beyer TD, Kolowos W, Heyder P, Kalden JR, Herrmann M (2001) Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ 8:327–334 DOI: 10.1038/sj.cdd.4400826
59. Gaipl US, Beyer TD, Baumann I, Voll RE, Stach CM, Heyder P, Kalden JR, Manfredi A, Herrmann M (2003) Exposure of anionic phospholipids serves as anti-inflammatory and immunosuppressive signal—implications for antiphospholipid syndrome and systemic lupus erythematosus. Immunobiology 207:73–81 DOI: 10.1078/0171-2985-00217
60. Gaipl US, Beyer TD, Heyder P, Kuenkele S, Bottcher A, Voll RE, Kalden JR, Herrmann M (2004) Cooperation between C1q and DNase I in the clearance of necrotic cell-derived chromatin. Arthritis Rheum 50:640–649 DOI: 10.1002/art.20034
61. Gaipl US, Voll RE, Sheriff A, Franz S, Kalden JR, Herrmann M (2005) Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun Rev 4:189–194 DOI: 10.1016/j.autrev.2004.10.007
62. Gaipl US, Kuhn A, Sheriff A, Munoz LE, Franz S, Voll RE, Kalden JR, Herrmann M (2006) Clearance of apoptotic cells in human SLE. Curr Dir Autoimmun 9:173–187
63. Gaipl US, Sheriff A, Franz S, Munoz LE, Voll RE, Kalden JR, Herrmann M (2006) Inefficient clearance of dying cells and autoreactivity. Curr Top Microbiol Immunol 305:161–176 DOI: 10.1007/3-540-29714-6_8
64. Gaipl US, Munoz LE, Grossmayer G, Lauber K, Franz S, Sarter K, Voll RE, Winkler T, Kuhn A, Kalden J, Kern P, Herrmann M (2007) Clearance deficiency and systemic lupus erythematosus (SLE). J Autoimmun 28:114–121 DOI: 10.1016/j.jaut.2007.02.005
65. Gasser O, Schifferli JA (2004) Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 104:2543–2548 DOI: 10.1182/blood-2004-01-0361
66. Gehrmann M, Liebisch G, Schmitz G, Anderson R, Steinem C, De Maio A, Pockley G, Multhoff G (2008) Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. PLoS ONE 3:e1925 DOI: 10.1371/journal.pone.0001925
67. Gidon-Jeangirard C, Hugel B, Holl V, Toti F, Laplanche JL, Meyer D, Freyssinet JM (1999) Annexin V delays apoptosis while exerting an external constraint preventing the release of CD4+ and PrPc+ membrane particles in a human T lymphocyte model. J Immunol 162:5712–5718
68. Giusti I, D'Ascenzo S, Millimaggi D, Taraboletti G, Carta G, Franceschini N, Pavan A, Dolo V (2008) Cathepsin B mediates the pH-dependent proinvasive activity of tumor-shed microvesicles. Neoplasia 10:481–488
69. Hampton MB, Vanags DM, Porn-Ares MI, Orrenius S (1996) Involvement of extracellular calcium in phosphatidylserine exposure during apoptosis. FEBS Lett 399:277–282 DOI: 10.1016/S0014-5793(96)01341-5
70. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187 DOI: 10.1038/417182a
71. He J, Yin Y, Luster TA, Watkins L, Thorpe PE (2009) Antiphosphatidylserine antibody combined with irradiation damages tumor blood vessels and induces tumor immunity in a rat model of glioblastoma. Clin Cancer Res 15:6871–6880 DOI: 10.1158/1078-0432.CCR-09-1499
72. Hoffmann PR, deCathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, Ridley AJ, Fadok VA, Henson PM (2001) Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol 155:649–659 DOI: 10.1083/jcb.200108080
73. Horakova E, Gasser O, Sadallah S, Inal JM, Bourgeois G, Ziekau I, Klimkait T, Schifferli JA (2004) Complement mediates the binding of HIV to erythrocytes. J Immunol 173:4236–4241
74. Horino K, Nishiura H, Ohsako T, Shibuya Y, Hiraoka T, Kitamura N, Yamamoto T (1998) A monocyte chemotactic factor, S19 ribosomal protein dimer, in phagocytic clearance of apoptotic cells. Lab Invest 78:603–617
75. Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin. Physiol (Bethesda) 20:22–27 DOI: 10.1152/physiol.00029.2004
76. 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
77. Idzko M, Hammad H, van Nimwegen M, Kool M, Willart MA, Muskens F, Hoogsteden HC, Luttmann W, Ferrari D, Di Virgilio F, Virchow JC Jr, Lambrecht BN (2007) Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med 13:913–919 DOI: 10.1038/nm1617
78. Ishimoto Y, Ohashi K, Mizuno K, Nakano T (2000) Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem 127:411–417
79. Janmey PA, Kinnunen PK (2006) Biophysical properties of lipids and dynamic membranes. Trends Cell Biol 16:538–546 DOI: 10.1016/j.tcb.2006.08.009
80. Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS (2003) Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res 109:175–180 DOI: 10.1016/S0049-3848(03)00064-1
81. Jinushi M, Sato M, Kanamoto A, Itoh A, Nagai S, Koyasu S, Dranoff G, Tahara H (2009) Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms. J Exp Med 206:1317–1326 DOI: 10.1084/jem.20082614
82. Kagan VE, Borisenko GG, Serinkan BF, Tyurina YY, Tyurin VA, Jiang J, Liu SX, Shvedova AA, Fabisiak JP, Uthaisang W, Fadeel B (2003) Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine. Am J Physiol Lung Cell Mol Physiol 285:L1–L17
83. Kagan VE, Borisenko GG, Tyurina YY, Tyurin VA, Jiang J, Potapovich AI, Kini V, Amoscato AA, Fujii Y (2004) Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine. Free Radic Biol Med 37:1963–1985 DOI: 10.1016/j.freeradbiomed.2004.08.016
84. Kenis H, van Genderen H, Bennaghmouch A, Rinia HA, Frederik P, Narula J, Hofstra L, Reutelingsperger CP (2004) Cell surface-expressed phosphatidylserine and annexin A5 open a novel portal of cell entry. J Biol Chem 279:52623–52629 DOI: 10.1074/jbc.M409009200
85. Kenis H, van Genderen H, Deckers NM, Lux PA, Hofstra L, Narula J, Reutelingsperger CP (2006) Annexin A5 inhibits engulfment through internalization of PS-expressing cell membrane patches. Exp Cell Res 312:719–726 DOI: 10.1016/j.yexcr.2005.11.023
86. Kenis H, Zandbergen HR, Hofstra L, Petrov AD, Dumont EA, Blankenberg FD, Haider N, Bitsch N, Gijbels M, Verjans JW, Narula N, Narula J, Reutelingsperger CP (2010) Annexin A5 uptake in ischemic myocardium: demonstration of reversible phosphatidylserine externalization and feasibility of radionuclide imaging. J Nucl Med 51:259–267 DOI: 10.2967/jnumed.109.068429
87. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL (2005) Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res 11:1010–1020
88. Kim R, Emi M, Tanabe K (2005) Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses. Cancer Biol Ther 4:924–933 DOI: 10.1158/1535-7163.MCT-04-0293
89. Kim S, Bae DJ, Hong M, Park SY, Kim IS (2010) The conserved histidine in epidermal growth factor-like domains of stabilin-2 modulates pH-dependent recognition of phosphatidylserine in apoptotic cells. Int J Biochem Cell Biol 42:1154–1163 DOI: 10.1016/j.biocel.2010.03.024
90. Kobayashi T, Kouzaki H, Kita H (2010) Human eosinophils recognize endogenous danger signal crystalline uric acid and produce proinflammatory cytokines mediated by autocrine ATP. J Immunol 184:6350–6358 DOI: 10.4049/jimmunol.0902673
91. Kol MA, de Kroon AI, Killian JA, de Kruijff B (2004) Transbilayer movement of phospholipids in biogenic membranes. Biochemistry 43:2673–2681 DOI: 10.1021/bi036200f
92. Kolowos W, Gaipl US, Sheriff A, Voll RE, Heyder P, Kern P, Kalden JR, Herrmann M (2005) Microparticles shed from different antigen-presenting cells display an individual pattern of surface molecules and a distinct potential of allogeneic T-cell activation. Scand J Immunol 61:226–233 DOI: 10.1111/j.1365-3083.2005.01551.x
93. Koppler B, Cohen C, Schlondorff D, Mack M (2006) Differential mechanisms of microparticle transfer toB cells and monocytes: anti-inflammatory properties of microparticles. Eur J Immunol 36:648–660 DOI: 10.1002/eji.200535435
94. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nunez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G (2009) Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ 16:3–11 DOI: 10.1038/cdd.2008.150
95. Krysko DV, D'Herde K, Vandenabeele P (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11:1709–1726 DOI: 10.1007/s10495-006-9527-8
96. Kunisaki Y, Masuko S, Noda M, Inayoshi A, Sanui T, Harada M, Sasazuki T, Fukui Y (2004) Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor. Blood 103:3362–3364 DOI: 10.1182/blood-2003-09-3245
97. Lauber K, Bohn E, Krober SM, Xiao YJ, Blumenthal SG, Lindemann RK, Marini P, Wiedig C, Zobywalski A, Baksh S, Xu Y, Autenrieth IB, Schulze-Osthoff K, Belka C, Stuhler G, Wesselborg S (2003) Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717–730 DOI: 10.1016/S0092-8674(03)00422-7
98. Lauber K, Blumenthal SG, Waibel M, Wesselborg S (2004) Clearance of apoptotic cells: getting rid of the corpses. Mol Cell 14:277–287 DOI: 10.1016/S1097-2765(04)00237-0
99. Lemke G, Rothlin CV (2008) Immunobiology of the TAM receptors. Nat Rev Immunol 8:327–336 DOI: 10.1038/nri2303
100. Li MO, Sarkisian MR, Mehal WZ, Rakic P, Flavell RA (2003) Phosphatidylserine receptor is required for clearance of apoptotic cells. Science 302:1560–1563 DOI: 10.1126/science.1087621
101. Lima LG, Chammas R, Monteiro RQ, Moreira ME, Barcinski MA (2009) Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett 283:168–175 DOI: 10.1016/j.canlet.2009.03.041
102. Lorenz HM, Herrmann M, Winkler T, Gaipl U, Kalden JR (2000) Role of apoptosis in autoimmunity. Apoptosis 5:443–449 DOI: 10.1023/A:1009692902805
103. Lucas M, Stuart LM, Zhang A, Hodivala-Dilke K, Febbraio M, Silverstein R, Savill J, Lacy-Hulbert A (2006) Requirements for apoptotic cell contact in regulation of macrophage responses. J Immunol 177:4047–4054
104. Mantel F, Frey B, Haslinger S, Schildkopf P, Sieber R, Ott OJ, Lödermann B, Rödel F, Sauer R, Fietkau R, Gaipl US (2010) Combination of ionising irradiation and hyperthermia activates programmed apoptotic and necrotic cell death pathways in human colorectal carcinoma cells. Strahlenther Onkol (in press)
105. Marques-da-Silva C, Burnstock G, Ojcius DM, Coutinho-Silva R (2010) Purinergic receptor agonists modulate phagocytosis and clearance of apoptotic cells in macrophages. Immunobiology. doi:10.1016/j.imbio.2010.03.010 DOI: 10.1016/j.imbio.2010.03.010
106. Mercer J, Helenius A (2008) Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells. Science 320:531–535 DOI: 10.1126/science.1155164
107. Mevorach D, Zhou JL, Song X, Elkon KB (1998) Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 188:387–392 DOI: 10.1084/jem.188.2.387
108. Mitchell JE, Cvetanovic M, Tibrewal N, Patel V, Colamonici OR, Li MO, Flavell RA, Levine JS, Birge RB, Ucker DS (2006) The presumptive phosphatidylserine receptor is dispensable for innate anti-inflammatory recognition and clearance of apoptotic cells. J Biol Chem 281:5718–5725 DOI: 10.1074/jbc.M509775200
109. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–439 DOI: 10.1038/nature06307
110. Mochizuki S, Okada Y (2007) ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628 DOI: 10.1111/j.1349-7006.2007.00434.x
111. Mortensen RF, Osmand AP, Lint TF, Gewurz H (1976) Interaction of C-reactive protein with lymphocytes and monocytes: complement-dependent adherence and phagocytosis. J Immunol 117:774–781
112. Munoz LE, Franz S, Pausch F, Furnrohr B, Sheriff A, Vogt B, Kern PM, Baum W, Stach C, von Laer D, Brachvogel B, Poschl E, Herrmann M, Gaipl US (2007) The influence on the immunomodulatory effects of dying and dead cells of Annexin V. J Leukoc Biol 81:6–14 DOI: 10.1189/jlb.0306166
113. Nakaya M, Tanaka M, Okabe Y, Hanayama R, Nagata S (2006) Opposite effects of rho family GTPases on engulfment of apoptotic cells by macrophages. J Biol Chem 281:8836–8842 DOI: 10.1074/jbc.M510972200
114. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61 DOI: 10.1038/nm1523
115. Ogden CA, Pound JD, Batth BK, Owens S, Johannessen I, Wood K, Gregory CD (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
116. Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL, Mandell JW, Ravichandran KS (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434 DOI: 10.1038/nature06329
117. Park SY, Jung MY, Kim HJ, Lee SJ, Kim SY, Lee BH, Kwon TH, Park RW, Kim IS (2008) Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 15:192–201 DOI: 10.1038/sj.cdd.4402242
118. Peter C, Waibel M, Radu CG, Yang LV, Witte ON, Schulze-Osthoff K, Wesselborg S, Lauber K (2008) Migration to apoptotic “find-me” signals is mediated via the phagocyte receptor G2A. J Biol Chem 283:5296–5305 DOI: 10.1074/jbc.M706586200
119. Peter C, Wesselborg S, Herrmann M, Lauber K (2010) Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells. Apoptosis 15:1007–1028 DOI: 10.1007/s10495-010-0472-1
120. Pilzer D, Gasser O, Moskovich O, Schifferli JA, Fishelson Z (2005) Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol 27:375–387 DOI: 10.1007/s00281-005-0004-1
121. Pomorski T, Hrafnsdottir S, Devaux PF, van Meer G (2001) Lipid distribution and transport across cellular membranes. Semin Cell Dev Biol 12:139–148 DOI: 10.1006/scdb.2000.0231
122. Pomorski T, Holthuis JC, Herrmann A, van Meer G (2004) Tracking down lipid flippases and their biological functions. J Cell Sci 117:805–813 DOI: 10.1242/jcs.01055
123. Ponner BB, Stach C, Zoller O, Hagenhofer M, Voll R, Kalden JR, Herrmann M (1998) Induction of apoptosis reduces immunogenicity of human T-cell lines in mice. Scand J Immunol 47:343–347 DOI: 10.1046/j.1365-3083.1998.00309.x
124. Poon IK, Hulett MD, Parish CR (2010) Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ 17:381–397 DOI: 10.1038/cdd.2009.195
125. Puddu P, Puddu GM, Cravero E, Muscari S, Muscari A (2010) The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases. Can J Cardiol 26:140–145 DOI: 10.1016/S0828-282X(10)70371-8
126. Qu Y, Franchi L, Nunez G, Dubyak GR (2007) Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 179:1913–1925
127. Rakoff-Nahoum S (2006) Why cancer and inflammation? Yale J Biol Med 79:123–130
128. Rigotti A, Acton SL, Krieger M (1995) The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem 270:16221–16224 DOI: 10.1074/jbc.270.32.18723
129. Rodriguez-Manzanet R, Sanjuan MA, Wu HY, Quintana FJ, Xiao S, Anderson AC, Weiner HL, Green DR, Kuchroo VK (2010) T and B cell hyperactivity and autoimmunity associated with niche-specific defects in apoptotic body clearance in TIM-4-deficient mice. Proc Natl Acad Sci USA 107:8706–8711 DOI: 10.1073/pnas.0910359107
130. Roelofsen B, van Meer G, Op den Kamp JA (1981) The lipids of red cell membranes. Compositional, structural and functional aspects. Scand J Clin Lab Invest Suppl 156:111–115 DOI: 10.3109/00365518109097442
131. Roelofsen B (1991) Molecular architecture and dynamics of the plasma membrane lipid bilayer: the red blood cell as a model. Infection 19 Suppl 4:S206–S209 DOI: 10.1007/BF01644035
132. Rosen A, Casciola-Rosen L (1999) Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ 6:6–12 DOI: 10.1038/sj.cdd.4400460
133. Sadallah S, Eken C, Schifferli JA (2008) Erythrocyte-derived ectosomes have immunosuppressive properties. J Leukoc Biol 84:1316–1325 DOI: 10.1189/jlb.0108013
134. Sanchez-Mejorada G, Rosales C (1998) Signal transduction by immunoglobulin Fc receptors. J Leukoc Biol 63:521–533
135. Santiago C, Ballesteros A, Martinez-Munoz L, Mellado M, Kaplan GG, Freeman GJ, Casasnovas JM (2007) Structures of T cell immunoglobulin mucin protein 4 show a metal-Ion-dependent ligand binding site where phosphatidylserine binds. Immunity 27:941–951 DOI: 10.1016/j.immuni.2007.11.008
136. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195 DOI: 10.1038/nature00858
137. Schifferli JA (2005) Complement: a member of the innate immune system. Springer Semin Immunopathol 27:273–275 DOI: 10.1007/s00281-005-0008-x
138. Schildkopf P, Frey B, Mantel F, Ott OJ, Weiss EM, Sieber R, Janko C, Sauer R, Fietkau R, Gaipl US (2010) Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells. Biochem Biophys Res Commun 391:1014–1020 DOI: 10.1016/j.bbrc.2009.12.008
139. Schilling D, Gehrmann M, Steinem C, De Maio A, Pockley AG, Abend M, Molls M, Multhoff G (2009) Binding of heat shock protein 70 to extracellular phosphatidylserine promotes killing of normoxic and hypoxic tumor cells. FASEB J 23:2467–2477 DOI: 10.1096/fj.08-125229
140. Schlegel RA, Williamson P (2007) P.S. to PS (phosphatidylserine)—pertinent proteins in apoptotic cell clearance. Sci STKE 2007:pe57 DOI: 10.1126/stke.4082007pe57
141. Schorn C, Janko C, Munoz L, Schulze C, Strysio M, Schett G, Herrmann M (2009) Sodium and potassium urate crystals differ in their inflammatory potential. Autoimmunity 42:314–316 DOI: 10.1080/08916930902832058
142. Schutters K, Reutelingsperger C (2010) Phosphatidylserine targeting for diagnosis and treatment of human diseases. Apoptosis 15:1072–1082 DOI: 10.1007/s10495-010-0503-y
143. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, Earp HS, Matsushima GK (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207–211 DOI: 10.1038/35075603
144. Segundo C, Medina F, Rodriguez C, Martinez-Palencia R, Leyva-Cobian F, Brieva JA (1999) Surface molecule loss and bleb formation by human germinal center B cells undergoing apoptosis: role of apoptotic blebs in monocyte chemotaxis. Blood 94:1012–1020
145. Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR (2003) Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 63:4331–4337
146. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521 DOI: 10.1038/nature01991
147. Silva MT, do Vale A, dos Santos NM (2008) Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications. Apoptosis 13:463–482 DOI: 10.1007/s10495-008-0187-8
148. Simak J, Gelderman MP (2006) Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev 20:1–26 DOI: 10.1016/j.tmrv.2005.08.001
149. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 28:367–388 DOI: 10.1146/annurev.immunol.021908.132603
150. Sims PJ, Wiedmer T (2001) Unraveling the mysteries of phospholipid scrambling. Thromb Haemost 86:266–275
151. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731 DOI: 10.1126/science.175.4023.720
152. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476 DOI: 10.1038/ncb1800
153. Stadler K, Frey B, Munoz LE, Finzel S, Rech J, Fietkau R, Herrmann M, Hueber A, Gaipl US (2009) Photopheresis with UV-A light and 8-methoxypsoralen leads to cell death and to release of blebs with anti-inflammatory phenotype in activated and non-activated lymphocytes. Biochem Biophys Res Commun 386:71–76 DOI: 10.1016/j.bbrc.2009.05.130
154. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579
155. Truman LA, Ford CA, Pasikowska M, Pound JD, Wilkinson SJ, Dumitriu IE, Melville L, Melrose LA, Ogden CA, Nibbs R, Graham G, Combadiere C, Gregory CD (2008) CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 112:5026–5036 DOI: 10.1182/blood-2008-06-162404
156. Tyurina YY, Tyurin VA, Zhao Q, Djukic M, Quinn PJ, Pitt BR, Kagan VE (2004) Oxidation of phosphatidylserine: a mechanism for plasma membrane phospholipid scrambling during apoptosis? Biochem Biophys Res Commun 324:1059–1064 DOI: 10.1016/j.bbrc.2004.09.102
157. Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, Rovere-Querini P, Herrmann M, Voll RE (2008) Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 205:3007–3018 DOI: 10.1084/jem.20081165
158. van Genderen HO, Kenis H, Hofstra L, Narula J, Reutelingsperger CP (2008) Extracellular annexin A5: functions of phosphatidylserine-binding and two-dimensional crystallization. Biochim Biophys Acta 1783:953–963 DOI: 10.1016/j.bbamcr.2008.01.030
159. van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124 DOI: 10.1038/nrm2330
160. van Zandbergen G, Klinger M, Mueller A, Dannenberg S, Gebert A, Solbach W, Laskay T (2004) Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into macrophages. J Immunol 173:6521–6525
161. van Zandbergen G, Bollinger A, Wenzel A, Kamhawi S, Voll R, Klinger M, Muller A, Holscher C, Herrmann M, Sacks D, Solbach W, Laskay T (2006) Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum. Proc Natl Acad Sci USA 103:13837–13842 DOI: 10.1073/pnas.0600843103
162. van Zandbergen G, Luder CG, Heussler V, Duszenko M (2010) Programmed cell death in unicellular parasites: a prerequisite for sustained infection? Trends Parasitol 26:477–483 DOI: 10.1016/j.pt.2010.06.008
163. Vega VL, Rodriguez-Silva M, Frey T, Gehrmann M, Diaz JC, Steinem C, Multhoff G, Arispe N, De Maio A (2008) Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J Immunol 180:4299–4307
164. Veron P, Segura E, Sugano G, Amigorena S, Thery C (2005) Accumulation of MFG-E8/lactadherin on exosomes from immature dendritic cells. Blood Cells Mol Dis 35:81–88 DOI: 10.1016/j.bcmd.2005.05.001
165. Voelker DR (1996) Lipid assembly into cell membranes. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier Science, New York, pp 391–423 DOI: 10.1016/S0167-7306(08)60522-0
166. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351 DOI: 10.1038/37022
167. Weerheim AM, Kolb AM, Sturk A, Nieuwland R (2002) Phospholipid composition of cell-derived microparticles determined by one-dimensional high-performance thin-layer chromatography. Anal Biochem 302:191–198 DOI: 10.1006/abio.2001.5552
168. Wilkin F, Duhant X, Bruyns C, Suarez-Huerta N, Boeynaems JM, Robaye B (2001) The P2Y11 receptor mediates the ATP-induced maturation of human monocyte-derived dendritic cells. J Immunol 166:7172–7177
169. Williamson P, Schlegel RA (2002) Transbilayer phospholipid movement and the clearance of apoptotic cells. Biochim Biophys Acta 1585:53–63
170. Wittrup A, Zhang SH, Svensson KJ, Kucharzewska P, Johansson MC, Morgelin M, Belting M (2010) Magnetic nanoparticle-based isolation of endocytic vesicles reveals a role of the heat shock protein GRP75 in macromolecular delivery. Proc Natl Acad Sci U S A 107:13342–13347 DOI: 10.1073/pnas.1002622107
171. Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288 DOI: 10.1111/j.1365-2141.1967.tb08741.x
172. Wright PK (2008) Targeting vesicle trafficking: an important approach to cancer chemotherapy. Recent Pat Anticancer Drug Discov 3:137–147 DOI: 10.2174/157489208784638730
173. Wu Y, Tibrewal N, Birge RB (2006) Phosphatidylserine recognition by phagocytes: a view to a kill. Trends Cell Biol 16:189–197 DOI: 10.1016/j.tcb.2006.02.003
174. Xiao YQ, Freire-de-Lima CG, Schiemann WP, Bratton DL, Vandivier RW, Henson PM (2008) Transcriptional and translational regulation of TGF-beta production in response to apoptotic cells. J Immunol 181:3575–3585
175. Xie Y, Bai O, Yuan J, Chibbar R, Slattery K, Wei Y, Deng Y, Xiang J (2009) Tumor apoptotic bodies inhibit CTL responses and antitumor immunity via membrane-bound transforming growth factor-beta1 inducing CD8+ T-cell anergy and CD4+ Tr1 cell responses. Cancer Res 69:7756–7766 DOI: 10.1158/0008-5472.CAN-09-0496
176. Yamaguchi H, Takagi J, Miyamae T, Yokota S, Fujimoto T, Nakamura S, Ohshima S, Naka T, Nagata S (2008) Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus. J Leukoc Biol 83:1300–1307 DOI: 10.1189/jlb.1107730
177. Yoshida H, Kawane K, Koike M, Mori Y, Uchiyama Y, Nagata S (2005) Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437:754–758 DOI: 10.1038/nature03964
178. Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294(Pt 1):1–14
179. Zitvogel L, Kepp O, Kroemer G (2010) Decoding cell death signals in inflammation and immunity. Cell 140:798–804 DOI: 10.1016/j.cell.2010.02.015
180. Zwaal RF, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89:1121–1132
181. Zwaal RF, Comfurius P, Bevers EM (2005) Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci 62:971–988 DOI: 10.1007/s00018-005-4527-3