Apoptotic cell recognition receptors and scavenger receptors

Immunological Reviews

Volumn 269, Issue 1, 2016, Pages 44-59

  Penberthy, Kristen K ^a   Ravichandran, Kodi S ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Apoptosis; Apoptotic cells; BAI1; Phosphatidylserine; Scavenger receptors; Signaling

Indexed keywords

ALPHAVBETA5 INTEGRIN; CELL RECEPTOR; LIGAND; PATTERN RECOGNITION RECEPTOR; PHOSPHATIDYLSERINE; PHOSPHATIDYLSERINE RECOGNITION RECEPTOR BAI1; PROTEIN TYROSINE KINASE; RECEPTOR TYROSINE KINASE MERTK; SCAVENGER RECEPTOR; STABILIN 2; UNCLASSIFIED DRUG; ANGIOGENIC PROTEIN; BAI1 PROTEIN, HUMAN; MERTK PROTEIN, HUMAN; NERVE CELL ADHESION MOLECULE; ONCOPROTEIN; STAB2 PROTEIN, HUMAN; VITRONECTIN RECEPTOR;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; GENE; HUMAN; INFLAMMATION; NONHUMAN; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; METABOLISM;

ANGIOGENIC PROTEINS; ANIMALS; APOPTOSIS; CELL ADHESION MOLECULES, NEURONAL; HUMANS; PHAGOCYTOSIS; PHOSPHATIDYLSERINES; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, PATTERN RECOGNITION; RECEPTORS, SCAVENGER; RECEPTORS, VITRONECTIN; SIGNAL TRANSDUCTION;

EID: 84950118324     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12376     Document Type: Article

References (190)

1. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493-501.
2. Duvall E, Wyllie AH, Morris RG. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology 1985;56:351-358.
3. Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. PNAS 1979;76:333-337.
4. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-b, PGE2, and PAF. J Clin Invest 1998;101:890-898.
5. Voll R, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature 1997;390:350-351.
6. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recogntion of removal by macrophages. J Immunol 1992;148:2207-2216.
7. Fadok VA, et al. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol 1992;149:4029-4035.
8. Martin SJ, et al. 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 1995;182:1545-1556.
9. Das S, et al. Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. PNAS 2011;108:2136-2141.
10. Tamura Y, et al. FEEL-1 and FEEL-2 Are Endocytic Receptors for Advanced Glycation End Products. J Biol Chem 2003;278:12613-12617.
11. Harris EN, Weigel JA, Weigel PH. The Human Hyaluronan Receptor for Endocytosis (HARE/Stabilin-2) Is a Systemic Clearance Receptor for Heparin. J Biochem 2008;283:17341-17350.
12. Singh TD, et al. MEGF10 functions as a receptor for the uptake of amyloid-B. FEBS Lett 2010;584:3936-3942.
13. Meyers JH, et al. TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation. Nat Immunol 2005;6:455-464.
14. Ichimura T, Asseldonk EJPV, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest 2008;118:1657-1668.
15. Gonias SL, Campana WM. LDL Receptor Related Protein-1A. Am J Pathol 2014;184:18-27.
16. Kim HY, et al. A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans. J Clin Invest 2011;121:1111-1118.
17. Parthasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D. Macrophage Oxidation of Low Density Lipoprotein Generates a Modified Form Recognized by the Scavenger Receptor. Arterioscler Thromb Vasc Biol 1986;6:505-510.
18. Park D, et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 2007;450:430-434.
19. Ipseiz N, et al. The Nuclear Receptor Nr4a1 Mediates Anti-Inflammatory Effects of Apoptotic Cells. J Immunol 2014;192:4852-4858.
20. Reddy SM, et al. Phagocytosis of apoptotic cells by macrophages induces novel signaling events leading to cytokine-independent survival and inhibition of proliferation: activation of Akt and inhibition of extracellular signal-regulated kinases 1 and 2. J Immunol 2002;169:702-713.
21. Grau A, Tabib A, Grau I, Reiner I, Mevorach D. Apoptotic cells induce NF-κB and inflammasome negative signaling. PLoS ONE 2015;10:e0122440.
22. Freire-de-Lima CG, Xiao Y-Q, Gardai SJ, Bratton DL, Schiemann WP, Henson PM. Apoptotic cells, through transforming growth factor-, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem 2006;281:38376-38384.
23. McDonald PP, Fadok VA, Bratton DL, Henson PM. Transcriptional and Translational regulation of inflammatory mediator production by endogenous TGF-b in macrophages that have ingested apoptotic cells. J Immunol 1999;163:6164-6172.
24. Murshid A, Borges TJ, Calderwood SK. Emerging roles for scavenger receptor SREC-I in immunity. Cytokine 2015;75:256-260.
25. Uchida Y, et al. The emerging role of T cell immunoglobulin mucin-1 in the mechanism of liver ischemia and reperfusion injury in the mouse. Hepatology 2009;51:1363-1372.
26. Gebhardt C, et al. RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 2008;205:275-285.
27. Canton J, Neculai D, Grinstein S. Scavenger receptors in homeostasis and immunity. Nat Rev Immunol 2013;13:621-634.
28. Feigelstock D, Thompson P, Mattoo P, Zhang Y, Kaplan GG. The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor. J Virol 1998;72:6621-6628.
29. He M, et al. Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells. EMBO Rep 2011;12:358-364.
30. PrabhuDas M, et al. Standardizing scavenger receptor nomenclature. J Immunol 2014;192:1997-2006.
31. Flannagan RS, Canton J, Furuya W, Glogauer M, Grinstein S. The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis. Mol Biol Cell 2014;25:1511-1522.
32. Wu Y, Singh S, Georgescu M-M, Birge RB. A role for Mer tyrosine kinase in avb5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci 2005;118:539-553.
33. Kim S, et al. Cross talk between engulfment receptors stabilin-2 and integrin avb5 orchestrates engulfment of phosphatidylserine-exposed erythrocytes. Mol Cell Biol 2012;32:2698-2708.
34. Ellis RE, Jacobson DM, Horvitz HR. Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 1991;129:79-94.
35. Nolan KM, Barrett K, Lu Y, Hu K-Q, Vincent S, Settleman J. Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes. Genes Dev 1998;12:3337-3342.
36. Hedgecock EM, Sulston JE, Thomson JN. Mutations affecting programmed cell deaths in the nematode caenorhabditis elegans. Science 1983;220:1277-1279.
37. Franc NC, Dimarcq JL, Lagueux M, Hoffmann J, Ezekowitz RA. Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity 1996;4:431-443.
38. Franc NC, Heitzler P, Ezekowitz RA, White K. Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila. Science 1999;284:1991-1994.
39. Sulston JE, Schierenberg E, White JG, Thomson JN. The embryonic cell lineage of the nematode Caenorhabditis elegans. Development 1983;100:64-119.
40. Sulston JE, Horvitz HR. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Development 1977;56:110-156.
41. Sulston JE. Post-embryonic development in the ventral cord of Caenorhabditis elegans. Philos Trans R Soc Lond 1976;275:287-297.
42. Callebaut I, Mignotte V, Souchet M, Mornon J-P. EMI domains are widespread and reveal the probable orthologs of the Caenorhabditis elegans CED-1 protein. Biochem J 2003;300:619-623.
43. Reddien PW, Horvitz HR. CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol 2000;2:131-136.
44. Hamon Y, et al. Cooperation between engulfment receptors: the case of ABCA1 and MEGF10. PLoS ONE 2006;1:e120.
45. Wu H-H, et al. Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Nat Neurosci 2009;12:1534-1541.
46. Wu Y-C, Horvitz HRC. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 1998;392:501-504.
47. Liu QA, Hengartner MO. Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6. Curr Biol 1999;9:1347-1350.
48. Wu Y-C, Horvitz HR. The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 1998;93:951-960.
49. Hasegawa H, et al. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol 1996;16:1-7.
50. Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev 1998;12:3331-3336.
51. Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 1999;68:459-486.
52. Erickson JW, Cerione RA. Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes. Biochemistry 2004;43:837-842.
53. Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product. Nature 1991;354:311-314.
54. Ron D, et al. A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr. New Biol 1991;3:372-379.
55. Hart MJ, et al. Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. J Biol Chem 1994;269:62-65.
56. Gumienny TL, et al. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 2001;107:27-41.
57. Brugnera E, et al. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 2002;4:574-582.
58. Wu Y-C, Tsai M-C, Cheng L-C, Chou C-J, Weng N-Y. CED-12 acts in the conserved CrkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Dev Cell 2001;1:491-502.
59. Zhou Z, Caron E, Hartwieg E, Hall A, Horvitz HR. The C. elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway. Dev Cell 2001;1:477-489.
60. Côté J-F, Vuori K. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci 2002;115:4901-4913.
61. Kunisaki Y, et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol 2006;174:647-652.
62. Sanz-Moreno V, et al. Rac activation and inactivation control plasticity of tumor cell movement. Cell 2008;135:510-523.
63. Hiramoto K, Negishi M, Katoh H. Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. Exp Cell Res 2006;312:4205-4216.
64. Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth. Exp Cell Res 2007;313:791-804.
65. Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L. The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron 2006;51:727-739.
66. Ruiz-Lafuente N, et al. Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells. Biol Open 2015;4:627-635.
67. Stevenson C, et al. Essential role of Elmo1 in Dock2-dependent lymphocyte migration. J Immunol 2014;192:6062-6070.
68. Namekata K, et al. Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. Genes Cells 2012;17:688-697.
69. Grimsley CM, et al. Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J Biol Chem 2004;279:6087-6097.
70. Lu M, et al. A steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs. Curr Biol 2005;15:371-377.
71. Lu M, et al. PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Nat Struct Mol Biol 2004;11:756-762.
72. Hamann J, et al. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev 2015;67:338-367.
73. Nishimori H, et al. A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 1997;15:2145-2150.
74. Manodori AB, Barabino GA, Lubin BH, Kuypers FA. Adherence of phosphatidylserine-exposing erythrocytes matrix thrombospondin. Blood 2000;95:1293-1300.
75. Gayen Betal, Setty BNY. Phosphatidylserine-positive erythrocytes bind to immobilized and soluble thrombospondin-1 via its heparin-binding domain. Transl Res 2008;152:165-177.
76. Tosello-Trampont A, Brugnera E, Ravichandran KS. Evidence for a conserved role for CrkII and Rac in engulfment of apoptotic cells. J Biol Chem 2001;276:13797-13802.
77. Akakura S, et al. C-terminal SH3 domain of CrkII regulates the assembly and function of the DOCK180/ELMO Rac-GEF. J Cell Physiol 2005;204:344-351.
78. Feller SM. Crk family adaptors - signalling complex formation and biological roles. Oncogene 2001;20:6348-6371.
79. Tosello-Trampont AC, Kinchen JM, Brugnera E, Haney LB, Hengartner MO, Ravichandran KS. Identification of two signaling submodules within the CrkII/ELMO/Dock180 pathway regulating engulfment of apoptotic cells. Cell Death Differ 2007;276:13797-13802.
80. Gauthier-Rouvière C, Vignal E, Mériane M, Roux P, Montcourier P, Fort P. RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. Mol Biol Cell 1998;9:1379-1394.
81. Katoh H, et al. Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells. Mol Cell Biol 2000;20:7378-7387.
82. Katoh H, Hiramoto K, Negishi M. Activation of Rac1 by RhoG regulates cell migration. J Cell Sci 2006;119:56-65.
83. Blangy A, Vignal E, Schmidt S, Debant A, Gauthier-Rouvière C, Fort P. TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of RhoG. J Cell Sci 2000;113:729-739.
84. Katoh H, Negishi M. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature 2003;424:461-464.
85. Kim J-Y, Oh MH, Bernard LP, Macara IG, Zhang H. The RhoG/ELMO1/Dock180 signaling module is required for spine morphogenesis in hippocampal neurons. J Biol Chem 2011;286:37615-37624.
86. deBakker CD, et al. 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 2004; 14: 2208-2216.
87. Tzircotis G, Braga VMM, Caron E. RhoG is required for both Fc R- and CR3-mediated phagocytosis. J Cell Sci 2011;124:2897-2902.
88. Martínez-Martín N, et al. T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis. Immunity 2011;35:208-222.
89. Tosello-Trampont AC, Nakada-Tsukui K, Ravichandran KS. Engulfment of apoptotic cells is negatively regulated by rho-mediated signaling. J Biol Chem 2003;278:49911-49919.
90. Vandivier RW, et al. Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences. Am J Physiol Lung Cell Mol Physiol 2009;297:L677-L686.
91. Richens TR, et al. Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA. Am J Respir Crit Care Med 2009;179:1011-1021.
92. Nakaya M, Tanaka M, Okabe Y, Hanayama R, Nagata S. Opposite effects of Rho family GTPases on engulfment of apoptotic cells by macrophages. J Biol Chem 2006;281:8836-8842.
93. Caron E, Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 1998;282:1717-1721.
94. Olazabal IM, Caron E, May RC, Schilling K, Knecht DA, Machesky LM. Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcyR, phagocytosis. Curr Biol 2002;12:1413-1418.
95. Wiedemann A, Patel JC, Lim J, Tsun A, van Kooyk Y, Caron E. Two distinct cytoplasmic regions of the 2 integrin chain regulate RhoA function during phagocytosis. J Cell Biol 2006;172:1069-1079.
96. Shi Y, et al. Protein-tyrosine kinase Syk is required for pathogen engulfment in complement-mediated phagocytosis. Blood 2006;107:1-10.
97. Kim JG, et al. Ras-related GTPases Rap1 and RhoA collectively induce the phagocytosis of serum-opsonized zymosan particles in macrophages. J Biol Chem 2012;287:5145-5155.
98. Kim J-S, et al. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages. Exp Mol Med 2005;37:575-587.
99. Moon M-Y, et al. Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides. Cell Signal 2013;25:1861-1869.
100. Kim JS, Diebold BA, Kim JI, Kim J, Lee JY, Park JB. Rho is involved in superoxide formation during phagocytosis of opsonized zymosans. J Biol Chem 2004;279:21589-21597.
101. Li Y, et al. Small GTPases Rap1 and RhoA regulate superoxide formation by Rac1 GTPases activation during the phagocytosis of IgG-opsonized zymosans in macrophages. Free Radic Biol Med 2012;52:1796-1805.
102. Garabuczi É, Sarang Z, Szondy Z. Glucocorticoids enhance prolonged clearance of apoptotic cells by upregulating liver X receptor, peroxisome proliferator-activated receptor-δ and UCP2. BBA Mol Cell Res 2014;1853:573-582.
103. Park D, et al. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature 2011;477:220-224.
104. Arsenijevic D, et al. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 2000;26:435-439.
105. de Bilbao F, et al. Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels. J Neurochem 2004;89:1283-1292.
106. Růžička M, et al. Recruitment of mitochondrial uncoupling protein UCP2 after lipopolysaccharide induction. Int J Biochem Cell Biol 2005;37:809-821.
107. Hochreiter-Hufford AE, et al. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 2013;497:263-267.
108. Fond AM, Lee CS, Schulman IG, Kiss RS, Ravichandran KS. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1. J Clin Invest 2015;125:2748-2758.
109. Bi X, et al. Myeloid cell-specific ATP-binding cassette transporter A1 deletion has minimal impact on atherogenesis in atherogenic diet-fed low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 2014;34:1888-1899.
110. Elliott MR, et al. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature 2011;467:333-337.
111. Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998;9:411-416.
112. Nakagawa A, Shiratsuchi A, Tsuda K, Nakanishi Y. In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. Mol Reprod Dev 2005;71:166-177.
113. Park T-J, Boyd K, Curran T. Cardiovascular and craniofacial defects in Crk-null mice. Mol Cell Biol 2006;26:6272-6282.
114. Laurin M, Fradet N, Blangy A, Hall A, Vuori K, Côté J-F. The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo. PNAS 2008;105:15446-15451.
115. Sanematsu F, et al. DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. Circ Res 2010;107:1102-1105.
116. Sugihara K, et al. Rac1 is required for the formation of three germ layers during gastrulation. Oncogene 1998;17:3427-3433.
117. Fiedler LR. Rac1 regulates cardiovascular development and postnatal function of endothelium. Cell Adh Migr 2009;3:143-145.
118. Tan W, Palmby TR, Gavard J, Amornphimoltham P, Zheng Y, Gutkind JS. An essential role for Rac1 in endothelial cell function and vascular development. FASEB J 2008;22:1829-1838.
119. Glogauer M, et al. Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions. J Immunol 2003;170:5652-5657.
120. Gu Y, et al. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 2003;302:445-449.
121. Juncadella IJ, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature 2012;493:547-551.
122. Hamon Y, et al. ABC1 promotes engulfment ofapoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2000;2:399-406.
123. Luciani M-F, Chimini G. The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death. EMBO J 1996;15:226-235.
124. Kiss RS, Elliott MR, Ma Z, Marcel YL, Ravichandran KS. Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes. Curr Biol 2006;16:2252-2258.
125. Yvan-Charvet L, et al. ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circ Res 2010;106:1861-1869.
126. Kinchen JM, et al. Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature 2005;434:93-99.
127. Zhou L, Choi HY, Li W-P, Xu F, Herz J. LRP1 controls cPLA2 phosphorylation, ABCA1 expression and cellular cholesterol export. PLoS ONE 2009;4:e6853.
128. Su HP, et al. 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 2002;277:11772-11779.
129. Park SY, Kim SY, Jung MY, Bae DJ, Kim IS. Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance. Mol Cell Biol 2008;28:5288-5298.
130. Park S-Y, Kang K-B, Thapa N, Kim S-Y, Lee S-J, Kim I-S. Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment. J Biol Chem 2008;283:10593-10600.
131. Osada Y, Sunatani T, Kim IS, Nakanishi Y, Shiratsuchi A. Signalling pathway involving GULP, MAPK and Rac1 for SR-BI-induced phagocytosis of apoptotic cells. J Biochem 2009;145:387-394.
132. Albert ML, Kim J-I, Birge RB. avB5 integrin recruits the CrkII-Dock180-Rac1 complex for phagocytosis of apoptotic cells. Nat Cell Biol 2000;2:899-905.
133. Akakura S, et al. The opsonin MFG-E8 is a ligand for the αvβ5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Exp Cell Res 2004;292:403-416.
134. Suzuki E, Nakayama M. The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern. Exp Cell Res 2007;313:2451-2464.
135. Zhou Z, Hartwieg E, Horvitz HR. CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 2001;104:43-56.
136. Scheib JL, Sullivan CS, Carter BD. Jedi-1 and MEGF10 signal engulfment of apoptotic neurons through the tyrosine kinase Syk. J Neurosci 2012;32:13022-13031.
137. Shi J, Heegaard CW, Rasmussen JT, Gilbert GE. Lactadherin binds selectively to membranes containing phosphatidyl-l-serine and increased curvature. BBA Biomembranes 2004;1667:82-90.
138. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature 2002;417:182-187.
139. Andersen MH, Berglund L, Rasmussen JT, Petersen TE. Bovine PAS-6/7 binds avb5 integrin and anionic phospholipids through two domains. Biochemistry 1997;36:5441-5446.
140. Andersen MH, Graversen H, Fedosov SN, Petersen TE, Rasmussen JT. Functional analyses of two cellular binding domains of bovine lactadherin. Biochemistry 2000;39:6200-6206.
141. Hsu T-Y, Wu Y-C. Engulfment of apoptotic cells in C. elegans is mediated by integrin a/SRC signaling. Curr Biol 2010;20:477-486.
142. Shah PP, Fong MY, Kakar SS. PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene 2011;31:3124-3135.
143. Caberoy NB, Zhou Y, Li W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J 2010;29:3898-3910.
144. Burstyn-Cohen T, Lew ED, Través PG, Burrola PG, Hash JC, Lemke G. Genetic dissection of TAM receptor-ligand interaction in retinal pigment epithelial cell phagocytosis. Neuron 2012;76:1123-1132.
145. Lew ED, et al. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. eLife 2014;3:e03385.
146. Tibrewal N, et al. Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kB transcriptional activation. J Biol Chem 2008;283:3618-3627.
147. Todt JC, Hu B, Curtis JL. The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. J Leukoc Biol 2004;75:705-713.
148. Abu-Thuraia A, et al. Axl phosphorylates elmo scaffold proteins to promote Rac activation and cell invasion. Mol Cell Biol 2014;35:76-87.
149. Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab 2006;4:211-221.
150. Moore KJ, et al. A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem 2002;277:47373-47379.
151. Stewart CR, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 2010;11:155-161.
152. Davis SP, Lee K, Gillrie MR, Roa L, Amrein M, Ho M. CD36 recruits αβ1 integrin to promote cytoadherence of P. falciparum-infected erythrocytes. PLoS Pathog 2013;9:e1003590.
153. Stuart LM, et al. Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain. J Cell Biol 2005;170:477-485.
154. Heit B, et al. Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization. Dev Cell 2013;24:372-383.
155. Finnemann SC, Silverstein RL. Differential roles of CD36 and avb5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J Exp Med 2001;194:1289-1298.
156. Jeannin P, et al. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity 2005;22:551-560.
157. Murshid A, Gong J, Prince T, Borges TJ, Calderwood SK. Scavenger receptor SREC-I mediated entry of TLR4 into lipid microdomains and triggered inflammatory cytokine release in RAW 264.7 cells upon LPS activation. PLoS ONE 2015;10:e0122529.
158. Bowdish DME, et al. MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis. PLoS Pathog 2009;5:e1000474.
159. Kissick HT, Dunn LK, Ghosh S, Nechama M, Kobzik L, Arredouani MS. The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. PLoS ONE 2014;9:e104148.
160. Todt JC, Hu B, Curtis JL. The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages. J Leukoc Biol 2008;84:510-518.
161. Mazaheri F, et al. Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia. Nat Commun 2014;5:1-11.
162. Kiefer C, Sumser E, Wernet MF, Von Lintig J. A class B scavenger receptor mediates the cellular uptake of carotenoids in Drosophila. Proc Natl Acad Sci USA 2002;99:10581-10586.
163. Pearson A, Lux A, Krieger M. Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster. Proc Natl Acad Sci USA 1995;92:4056-4060.
164. Silva EA, Burden J, Franc NC. In vivo and in vitro methods for studying apoptotic cell engulfment in Drosophila. Methods Enzymol 2008;446:39-59.
165. Cuttell L, et al. Undertaker, a Drosophila Junctophilin, links Draper-mediated phagocytosis and calcium homeostasis. Cell 2008;135:524-534.
166. Silva E, Au-Yeung HW, Van Goethem E, Burden J, Franc NC. Requirement for a Drosophila E3-ubiquitin ligase in phagocytosis of apoptotic cells. Immunity 2007;27:585-596.
167. Lanoue V, et al. The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons. Mol Psychiatry 2013;18:943-950.
168. Hamoud N, Tran V, Croteau LP, Kania A, Cote JF. G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates. PNAS 2014;111:3745-3750.
169. Curtiss ML, et al. Fyn binds to and phosphorylates T cell immunoglobulin and mucin domain-1 (Tim-1). Mol Immunol 2011;48:1424-1431.
170. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature 2007;450:435-439.
171. Lu Q, et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature 1999;398:723-728.
172. Seitz HM, Camenisch TD, Lemke G, Earp HS, Matsushima GK. Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol 2007;178:5635-5642.
173. Zagórska A, Través PG, Lew ED, Dransfield I, Lemke G. Diversification of TAM receptor tyrosine kinase function. Nat Immunol 2014;15:920-928.
174. Adachi H, Tsujimoto M. FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities. J Biol Chem 2002;277:34264-34270.
175. Kzhyshkowska J, Gratchev A, Goerdt S. Stabilin-1, a homeostatic scavenger receptor with multiple functions. J Cell Mol Med 2006;10:635-649.
176. Politz O, et al. Stabilin-1 and -2 constitute a novel family of fasciclin-like hyaluronan receptor homologues. J Biochem Soc 2002;362:155-164.
177. Park SY, et al. Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages. J Cell Sci 2009;122:3365-3373.
178. Park S-Y, Kim S-Y, Kang K-B, Kim I-S. Adaptor protein GULP is involved in stabilin-1-mediated phagocytosis. Biochem J 2010;398:467-472.
179. Hirose Y, et al. Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis. PNAS 2012;109:4263-4268.
180. Park SY, et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 2007;15:192-201.
181. Zhou B, Weigel JA, Fauss L, Weigel PH. Identification of the hyaluronan receptor for endocytosis (HARE). J Biol Chem 2000;275:37733-37741.
182. Bu H-F, et al. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest 2007;117:3673-3683.
183. Lauber K, et al. Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids. Cell Death Differ 2013;20:1230-1240.
184. Savill J, Dransfield I, Hogg N, Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 1990;343:170-173.
185. Berwin B, Delneste Y, Lovingood RV, Post SR, Pizzo SV. SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J Biol Chem 2004;279:51250-51257.
186. Tamura Y, et al. Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide. J Biol Chem 2004;279:30938-30944.
187. Ramirez-Ortiz ZG, et al. The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity. Nat Immunol 2013;14:917-926.
188. Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 2001;108:779-784.
189. Wang X, et al. Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nat Cell Biol 2010;12:655-664.
190. Chung W-S, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 2013;504:394-400.