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Phagocytosis and Immunity

  • Steven Greenberg
Chapter
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Part of the Medical Intelligence Unit book series (MIUN)

Abstract

Phagocytosis is an phylogenetically conserved mechanism utilized by many cells to ingest microbial pathogens and apoptotic or necrotic corpses. Recent studies have demonstrated that phagocytosis serves to initiate immunity mediated by both Class I and Class II MHC. Depending on the identity of the specific phagocytic receptor involved, phagocytosis can either enhance or suppress inflammation. Dysregulation of phagocytosis can lead to alterations in the immune response and may contribute to autoimmunity. Harnessing the phagocytic capacity of antigen presenting cells may ultimately lead to exploitation of phagocytosis as a therapeutic modality in intractable diseases, such as advanced cancer.

Phagocytosis is the process by which leukocytes and other cells ingest particulate ligands whose size exceeds about 1 µm. This phylogenetically ancient cellular event is critical for both innate and acquired immunity. By ingesting microbial pathogens, phagocytic leukocytes accomplish two essential immune functions. First, they initiate a microbial death pathway. They target ingested pathogens to degradative organelles, such as lysosomes and to vesicles containing components of the phagocyte oxidase complex. Second, phagocytic leukocytes, particularly dendritic cells (DCs), utilize phagocytosis to direct antigens to both MHC I and II compartments. Thus, phagocytosis serves a dual role as an effector of innate immunity and an initiator of acquired immunity.

Keywords

Apoptotic Cell Focal Adhesion Kinase Phagosomal Membrane Phagocytic Receptor Haemophilus Ducreyi 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Franc NC, White K, Ezekowitz RAB. Phagocytosis and development: Back to the future. Curr Opin Immunol 1999; 11(1):47–52.PubMedGoogle Scholar
  2. 2.
    Greenberg S, Grinstein S. Phagocytosis and innate immunity. Curr Opin Immunol 2002; 14(1):136–145.PubMedGoogle Scholar
  3. 3.
    Garcia-Garcia E, Rosales C. Signal transduction during Fc receptor-mediated phagocytosis. J Leukoc Biol 2002; 72(6):1092–1108.PubMedGoogle Scholar
  4. 4.
    Fitzer-Attas CJ, Lowry M, Crowley MT et al. Fcγ receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn. J Exp Med 2000; 191(4):669–682.PubMedGoogle Scholar
  5. 5.
    Crowley MT, Costello PS, Fitzer-Attas CJ et al. A critical role for Syk in signal transduction and phagocytosis mediated by Fcγ receptors on macrophages. J Exp Med 1997; 186:1027–1039.PubMedGoogle Scholar
  6. 6.
    Cox D, Chang P, Kurosaki T et al. Syk tyrosine kinase is required for immunoreceptor tyrosine activation motif-dependent actin assembly. J Biol Chem 1996; 271(28):16597–16602.PubMedGoogle Scholar
  7. 7.
    Matsuda M, Park JG, Wang DC et al. Abrogation of the Fcγ receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides. Mol Biol Cell 1996; 7(7):1095–1106.PubMedGoogle Scholar
  8. 8.
    Kiefer F, Brumell J, Al-Alawi N et al. The Syk protein tyrosine kinase is essential for Fcγ receptor signaling in macrophages and neutrophils. Mol Cell Biol 1998; 18(7):4209–4220.PubMedGoogle Scholar
  9. 9.
    Cox D, Tseng C-C, Bjekic G et al. A requirement for phosphatidylinositol 3-kinase in pseudopod extension. J Biol Chem 1999; 274:1240–1247.PubMedGoogle Scholar
  10. 10.
    Ninomiya N, Hazeki K, Fukui Y et al. Involvement of phosphatidylinositol 3-kinase in Fcγ receptor signaling. J Biol Chem 1994; 269:22732–22737.PubMedGoogle Scholar
  11. 11.
    Araki N, Johnson MT, Swanson JA. A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol 1996; 135:1249–1260.PubMedGoogle Scholar
  12. 12.
    Botelho RJ, Teruel M, Dierckman R et al. Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis. J Cell Biol 2000; 151(7):1353–1368.PubMedGoogle Scholar
  13. 13.
    Mansfield PJ, Shayman JA, Boxer LA Regulation of polymorphonuclear leukocyte phagocytosis by myosin light chain kinase after activation of mitogen-activated protein kinase. Blood 2000; 95(7):2407–2412.PubMedGoogle Scholar
  14. 14.
    Larsen EC, DiGennaro JA, Saito N et al. Differential requirement for classic and novel PKC isoforms in respiratory burst and phagocytosis in RAW 264.7 cells. J Immunol 2000; 165(5):2809–2817.PubMedGoogle Scholar
  15. 15.
    Lennartz MR, Brown EJ. Arachidonic acid is essential for IgG Fc receptor-mediated phagocytosis by human monocytes. Journal of Immunology 1991; 147(2):621–626.Google Scholar
  16. 16.
    Kusner DJ, Hall CF, Jackson S. Fcγ receptor-mediated activation of phospholipase D regulates macrophage phagocytosis of IgG-opsonized particles. J Immunol 1999; 162:2266–2274.PubMedGoogle Scholar
  17. 17.
    Lennartz MR, Yuen AFC, Masi SM et al. Phospholipase A2 inhibition results in sequestration of plasma membrane into electron-lucent vesicles during IgG-mediated phagocytosis. J Cell Sci 1997; 110:2041–2052.PubMedGoogle Scholar
  18. 18.
    Mancuso P, Nana-Sinkam P, Peters-Golden M. Leukotriene B4 augments neutrophil phagocytosis of Klebsiella pneumoniae. Infect Immun 2001; 69(4):2011–2016.PubMedGoogle Scholar
  19. 19.
    Cox D, Chang P, Zhang Q et al. Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes. J Exp Med 1997; 186:1487–1494.PubMedGoogle Scholar
  20. 20.
    Forsberg M, Druid P, Zheng L et al. Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils. J Leukoc Biol 2003; 74(4):611–619, Epub 2003 Jul 2001.PubMedGoogle Scholar
  21. 21.
    Caron E, Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 1998; 282:1717–1721.PubMedGoogle Scholar
  22. 22.
    Massol P, Montcourrier P, Guillemot J-C et al. Fc receptor-mediated phagocytosis requires CDC42 and Racl. EMBO J 1998; 17:6219–6229.PubMedGoogle Scholar
  23. 23.
    Zhang Q, Cox D, Tseng C-C et al. A requirement for ARF6 in Fcγ receptor-mediated phagocytosis in macrophages. J Biol Chem 1998; 273:19977–19981.PubMedGoogle Scholar
  24. 24.
    Niedergang F, Colucci-Guyon E, Dubois T et al. ADP ribosylation factor 6 is activated and controls membrane delivery during phagocytosis in macrophages. J Cell Biol 2003; 161(6):1143–1150, Epub 2003 Jun 1116. Epub 2003 Jun 1116.PubMedGoogle Scholar
  25. 25.
    Cox D, Lee DJ, Dale BM et al. A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis. Proc Natl Acad Sci USA 2000; 97:680–685.PubMedGoogle Scholar
  26. 26.
    Hackam DJ, Rotstein OD, Sjolin C et al. v-SNAREdependent secretion is required for phagocytosis. Proc Natl Acad Sci USA 1998; 95(20):11691–11696.PubMedGoogle Scholar
  27. 27.
    Cox D, Berg JS, Cammer M et al. Myosin X is a downstream effector of PI(3)K during phagocytosis. Nature Cell Biology 2002; 4(7):469–477.PubMedGoogle Scholar
  28. 28.
    Steele C, Marrero L, Swain S et al. Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 β-glucan receptor. J Exp Med 2003; 198(11):1677–1688.PubMedGoogle Scholar
  29. 29.
    Schmitter T, Agerer F, Peterson L et al. Granulocyte CEACAM3 Is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens. J Exp Med 2004; 199(1):35–46.PubMedGoogle Scholar
  30. 30.
    McCaw SE, Schneider J, Liao EH et al. Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor. Mol Microbiol 2003; 49(3):623–637.PubMedGoogle Scholar
  31. 31.
    Shen Y, Naujokas M, Park M et al. InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell 2000; 103(3):501–510.PubMedGoogle Scholar
  32. 32.
    Braun L, Ghebrehiwet B, Cossart P. gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes. EMBO J 2000; 19(7):1458–1466.PubMedGoogle Scholar
  33. 33.
    Lecuit M, Hurme R, Pizarro-Cerda J et al. A role for α-and β-catenins in bacterial uptake. Proc Natl Acad Sci USA 2000; 97(18):10008–10013.PubMedGoogle Scholar
  34. 34.
    Mengaud J, Ohayon H, Gounon P et al. E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 1996; 84(6):923–932.PubMedGoogle Scholar
  35. 35.
    Alrutz MA, Isberg RR. Involvement of focal adhesion kinase in invasin-mediated uptake. Proc Natl Acad Sci USA 1998; 95(23):13658–13663.PubMedGoogle Scholar
  36. 36.
    Tran Van Nhieu G, Caron E, Hall A et al. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J 1999; 18(12):3249–3262.PubMedGoogle Scholar
  37. 37.
    Hardt W-D, Chen L-M, Schuebel KE et al. S. typimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 1998; 93:815–826.PubMedGoogle Scholar
  38. 38.
    Vakevainen M, Greenberg S, Hansen EJ. Inhibition of phagocytosis by Haemophilus ducreyi requires expression of the LspA1 and LspA2 proteins. Infect Immun 2003; 71(10):5994–6003.PubMedGoogle Scholar
  39. 39.
    Black DS, Bliska JB. Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. EMBO J 1997; 16(10):2730–2744.PubMedGoogle Scholar
  40. 40.
    Black DS, Bliska JB. The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence. Mol Microbiol 2000; 37(3):515–527.PubMedGoogle Scholar
  41. 41.
    Malik ZA, Denning GM, Kusner DJ. Inhibition of Ca2+ signaling by Mycobacterium tuberculosis is associated with reduced phagosome-lysosome fusion and increased survival within human macrophages. J Exp Med 2000; 191(2):287–302.PubMedGoogle Scholar
  42. 42.
    Fratti RA, Chua J, Vergne I et al. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci USA 2003; 100(9):5437–5442, Epub 2003 Apr 5417.PubMedGoogle Scholar
  43. 43.
    Russell DG. Phagosomes, fatty acids and tuberculosis. Nat Cell Biol 2003; 5(9):776–778.PubMedGoogle Scholar
  44. 44.
    Anes E, Kuhnel MP, Bos E et al. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol 2003; 5(9):793–802, Epub 2003 Aug 2024.PubMedGoogle Scholar
  45. 45.
    Clemens DL, Lee BY, Horwitz MA. Deviant expression of Rab5 on phagosomes containing the intracellular pathogens Mycobacterium tuberculosis and Legionella pneumophila is associated with altered phagosomal fate. Infec Immunity 2000; 68(5):2671–2684.Google Scholar
  46. 46.
    Horwitz MA, Maxfield FR. Legionella pneumophila inhibits acidification of its phagosome in human moncytes. J Cell Biol 1984; 99:1936–1943.PubMedGoogle Scholar
  47. 47.
    Horwitz M. Phagocytosis of the Legionnaires’ disease bacterium (Legionella pneumophila) occurs by a novel mechanism: Engulfment within a pseudopod coil. Cell 1984; 36:27–33.PubMedGoogle Scholar
  48. 48.
    Kagan JC, Roy CR. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol 2002; 4(12):945–954.PubMedGoogle Scholar
  49. 49.
    Harrison RE, Bucci C, Vieira OV et al. Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: Role of Rab7 and RILP. Mol Cell Biol 2003; 23(18):6494–6506.PubMedGoogle Scholar
  50. 50.
    Trombetta ES, Ebersold M, Garrett W et al. Activation of lysosomal function during dendritic cell maturation. Science 2003; 299(5611):1400–1403.PubMedGoogle Scholar
  51. 51.
    Bevan MJ. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med 1976; 143(5):1283–1288.PubMedGoogle Scholar
  52. 52.
    Thery C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol 2001; 13(1):45–51.PubMedGoogle Scholar
  53. 53.
    Guermonprez P, Saveanu L, Kleijmeer M et al. ER-phagosome fusion defines an MHC Class I cross-presentation compartment in dendritic cells. Nature 2003; 425(6956):397–402.PubMedGoogle Scholar
  54. 54.
    Houde M, Bertholet S, Gagnon E et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 2003; 425(6956):402–406.PubMedGoogle Scholar
  55. 55.
    Wiertz EJ, Tortorella D, Bogyo M et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 1996; 384(6608):432–438.PubMedGoogle Scholar
  56. 56.
    Sigal LJ, Crotty S, Andino R et al. Cytotoxic T-cell immunity to virus-infected nonhaematopoietic cells requires presentation of exogenous antigen. Nature 1999; 398(6722):77–80.PubMedGoogle Scholar
  57. 57.
    Freigang S, Egger D, Bienz K et al. Endogenous neosynthesis vs. Cross-presentation of viral antigens for cytotoxic T cell priming. Proc Natl Acad Sci USA 2003; 100(23):13477–13482, Epub 2003 Oct 13431.PubMedGoogle Scholar
  58. 58.
    Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392(6671):86–89.PubMedGoogle Scholar
  59. 59.
    Ochsenbein AF. Principles of tumor immunosurveillance and implications for immunotherapy. Cancer Gene Ther 2002; 9(12):1043–1055.PubMedGoogle Scholar
  60. 60.
    Arina A, Tirapu I, Alfaro C et al. Clinical implications of antigen transfer mechanisms from malignant to dendritic cells. Exploiting cross-priming. Exp Hematol 2002; 30(12):1355–1364.PubMedGoogle Scholar
  61. 61.
    Ward S, Casey D, Labarthe MC et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol Immunother 2002; 51(7):351–357, Epub 2002 Jun 2014.PubMedGoogle Scholar
  62. 62.
    Suto R, Srivastava PK. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 1995; 269(5230):1585–1588.PubMedGoogle Scholar
  63. 63.
    Mackey MF, Gunn JR, Maliszewsky C et al. Dendritic cells require maturation via CD40 to generate protective antitumor immunity. J Immunol 1998; 161(5):2094–2098.PubMedGoogle Scholar
  64. 64.
    Labeur MS, Roters B, Pers B et al. Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage. J Immunol 1999; 162(1):168–175.PubMedGoogle Scholar
  65. 65.
    Regnault A, Lankar D, Lacabanne V et al. Fcγ receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 1999; 189(2):371–380.PubMedGoogle Scholar
  66. 66.
    Rafiq K, Bergtold A, Clynes R. Immune complex-mediated antigen presentation induces tumor immunity. J Clin Invest 2002; 110(1):71–79.PubMedGoogle Scholar
  67. 67.
    Hoeppner DJ, Hengartner MO, Schnabel R. Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 2001; 412(6843):202–206.PubMedGoogle Scholar
  68. 68.
    Lauber K, Bohn E, Krober SM et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 2003; 113(6):717–730.PubMedGoogle Scholar
  69. 69.
    Binder RJ, Han DK, Srivastava PK. CD91: A receptor for heat shock protein gp96. Nat Immunol 2000; 1(2):151–155.PubMedGoogle Scholar
  70. 70.
    Vabulas RM, Wagner H, Schild H. Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol 2002; 270:169–184.PubMedGoogle Scholar
  71. 71.
    Gao B, Tsan MF. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages. J Biol Chem 2003; 278(1):174–179.PubMedGoogle Scholar
  72. 72.
    Fadok VA, Bratton DL, Konowal A et al. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF. J Clin Invest 1998; 101(4):890–898.PubMedGoogle Scholar
  73. 73.
    Bolland S, Ravetch JV. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 2000; 13(2):277–285.PubMedGoogle Scholar
  74. 74.
    Gardai SJ, Xiao YQ, Dickinson M et al. By binding SIRPá or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003; 115(1):13–23.PubMedGoogle Scholar
  75. 75.
    Vandivier RW, Ogden CA, Fadok VA et al. 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 2002; 169(7):3978–3986.PubMedGoogle Scholar
  76. 76.
    Oldenborg PA, Gresham HD, Lindberg FP. CD47-signal regulatory protein alpha (SIRP alpha) regulates Fc gamma and complement receptor-mediated phagocytosis. J Exp Med 2001; 193(7):855–861.PubMedGoogle Scholar
  77. 77.
    Oldenborg PA, Zheleznyak A, Fang YF et al. Role of CD47 as a marker of self on red blood cells. Science 2000; 288(5473):2051–2054.PubMedGoogle Scholar
  78. 78.
    Hart SP, Smith JR, Dransfield I. Phagocytosis of opsonized apoptotic cells: Roles for ‘old-fashioned’ receptors for antibody and complement. Clin Exp Immunol 2004; 135(2):181–185.PubMedGoogle Scholar
  79. 79.
    Taylor PR, Carugati A, Fadok VA et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 2000; 192(3):359–366.PubMedGoogle Scholar
  80. 80.
    Bickerstaff MC, Botto M, Hutchinson WL et al. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 1999; 5(6):694–697.PubMedGoogle Scholar
  81. 81.
    Cohen PL, Caricchio R, Abraham V et al. Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J Exp Med 2002; 196(1):135–140.PubMedGoogle Scholar
  82. 82.
    Paul E, Carroll MC. SAP-less chromatin triggers systemic lupus erythematosus. Nat Med 1999; 5(6):607–608.PubMedGoogle Scholar
  83. 83.
    Gershov D, Kim S, Brot N et al. 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 2000; 192(9):1353–1363.PubMedGoogle Scholar
  84. 84.
    Ghiran I, Barbashov SF, Klickstein LB et al. Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 2000; 192(12):1797–1808.PubMedGoogle Scholar
  85. 85.
    Ross GD. Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/αMβ2-integrin glycoprotein. Crit Rev Immunol 2000; 20(3):197–222.PubMedGoogle Scholar
  86. 86.
    Zaffran Y, Zhang L, Ellner JJ. Role of CR4 in Mycobacterium tuberculosis-human macrophages binding and signal transduction in the absence of serum. Infect Immun 1998; 66(9):4541–4544.PubMedGoogle Scholar
  87. 87.
    Malaviya R, Gao Z, Thankavel K et al. The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. Proc Natl Acad Sci USA 1999; 96(14):8110–8115.PubMedGoogle Scholar
  88. 88.
    Linehan SA, Martinez-Pomares L, Gordon S. Macrophage lectins in host defence. Microbes Infect 2000; 2(3):279–288.PubMedGoogle Scholar
  89. 89.
    Suzuki H, Kurihara Y, Takeya M et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 1997; 386(6622):292–296.PubMedGoogle Scholar
  90. 90.
    Platt N, Suzuki H, Kurihara Y et al. Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc Natl Acad Sci USA 1996; 93(22):12456–12460.PubMedGoogle Scholar
  91. 91.
    Thomas CA, Li Y, Kodama T et al. Protection from lethal gram-positive infection by macrophage scavenger receptor-dependent phagocytosis. J Exp Med 2000; 191(1):147–156.PubMedGoogle Scholar
  92. 92.
    Shiratsuchi A, Kawasaki Y, Ikemoto M et al. Role of class B scavenger receptor type I in phagocytosis of apoptotic rat spermatogenic cells by Sertoli cells. J Biol Chem 1999; 274(9):5901–5908.PubMedGoogle Scholar
  93. 93.
    Imachi H, Murao K, Hiramine C et al. Human scavenger receptor B1 is involved in recognition of apoptotic thymocytes by thymic nurse cells. Lab Invest 2000; 80(2):263–270.PubMedGoogle Scholar
  94. 94.
    Palecanda A, Paulauskis J, Al-Mutairi E et al. Role of the scavenger receptor MARCO in alveolar macrophage binding of unopsonized environmental particles. J Exp Med 1999; 189(9):1497–1506.PubMedGoogle Scholar
  95. 95.
    Scott RS, McMahon EJ, Pop SM et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 2001; 411(6834):207–211.PubMedGoogle Scholar
  96. 96.
    Fadok VA, Bratton DL, Rose DM et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 2000; 405(6782):85–90.PubMedGoogle Scholar
  97. 97.
    Savill J, Hogg N, Ren Y et al. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. Journal of Clinical Investigation 1992; 90(4):1513–1522.PubMedGoogle Scholar
  98. 98.
    Fadok VA, Warner ML, Bratton DL et al. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor αvβ3. J Immunol 1998; 161(11):6250–6257.PubMedGoogle Scholar
  99. 99.
    Heale J-P, Pollard AJ, Crookall K et al. Two distinct receptors mediate nonopsonic phagocytosis of different strains of Pseudomonas aeruginosa. J Infec Dis 2001; 183(8):1214–1220.Google Scholar
  100. 100.
    Devitt A, Moffatt OD, Raykundalia C et al. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 1998; 392(6675):505–509.PubMedGoogle Scholar
  101. 101.
    Isberg RR, Leong JM. Multiple β1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell 1990; 60(5):861–871.PubMedGoogle Scholar
  102. 102.
    Savill J, Dransfield I, Hogg N et al. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 1990; 343:170–173.PubMedGoogle Scholar
  103. 103.
    Albert ML, Pearce SF, Francisco LM et al. Immature dendritic cells phagocytose apoptotic cells via αvβ5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998; 188(7):1359–1368.PubMedGoogle Scholar
  104. 104.
    Finnemann SC, Rodriguez-Boulan E. Macrophage and retinal pigment epithelium phagocytosis: Apoptotic cells and photoreceptors compete for αvβ3 and αvβ5 integrins, and protein kinase C regulates αvβ5 binding and cytoskeletal linkage. J Exp Med 1999; 190(6):861–874.PubMedGoogle Scholar

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© Eurekah.com and Springer Science+Business Media 2005

Authors and Affiliations

  • Steven Greenberg
    • 1
  1. 1.Departments of Medicine and PharmacologyColumbia UniversityNew YorkUSA

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