Diversity in Phagocytic Signaling

A Story of Greed, Sharing, and Exploitation
  • Erick García-García
Part of the Medical Intelligence Unit book series (MIUN)


Phagocytosis is the process whereby cells engulf large particles. Phagocytosis is triggered by the interaction of opsonins covering the surface of a phagocytic target with specific phagocyte receptors. In multicellular organisms phagocytosis participates in tissue remodeling and contributes to homeostasis. Higher organisms possess various phagocytic systems. Each system is composed of a series of ligands, specific receptors, and signaling pathways that culminate in particle internalization and destruction. The best studied phagocytic system is that of the receptors that bind to the Fc portion of immunoglobulins. Other phagocytic systems include phagocytosis of complement-opsonized particles, and phagocytosis of apoptotic cells. The signaling pathways elicited by many phagocytic receptors are complex and diverse. Comparison between the signaling pathways elicited by many phagocytic receptors shows that phagocytic signaling pathways share many elements. Shared signaling molecules include tyrosine kinases, lipid kinases, phospholipases, and serine/threonine kinases. Additionally, all phagocytic signaling pathways activate cytoskeleton-remodeling molecules. The dynamic nature of the cytoskeleton is thus exploited by all phagocytic systems to achieve particle internalization. In this review I will discuss the connections between the various signaling pathways of different phagocytic systems, and the regulation of cytoskeleton dynamics as a means to achieve particle internalization.


Apoptotic Cell Arachidonic Acid Release Leukoc Biol Actin Fiber Particle Internalization 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jones SL, Lindberg FP, Brown EJ. Phagocytosis. In: Paul WE, ed. Fundamental Immunology. 4th ed. Philadelphia: Lippincott-Raven Publishers, 1999:997–1020.Google Scholar
  2. 2.
    Rabinovitch M. Professional and nonprofessional phagocytes: An introduction. Trends in Cell Biology 1995; 5:85–87.PubMedCrossRefGoogle Scholar
  3. 3.
    Rubartelli A, Poggi A, Zocchi MR. The selective engulfment of apoptotic bodies by dendritic cells is mediated by the alpha(v)beta3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 1997; 27:1893–900.PubMedCrossRefGoogle Scholar
  4. 4.
    Albert ML, Pearce SF, Francisco LM et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998; 188:1359–68.PubMedCrossRefGoogle Scholar
  5. 5.
    Fadok VA, Bratton DL, Rose DM et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 2000; 405:85–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Witting A, Muller P, Herrmann A et al. Phagocytic clearance of apoptotic neurons by Microglia/Brain macrophages in vitro: Involvement of lectin-, integrin-, and phosphatidylserine-mediated recognition. J Neurochem 2000; 75:1060–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Ryeom SW, Sparrow JR, Silverstein RL. CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J Cell Sci 1996; 109 (Pt 2):387–95.PubMedGoogle Scholar
  8. 8.
    Parnaik R, Raff MC, Scholes J. Differences between the clearance of apoptotic cells by professional and nonprofessional phagocytes. Curr Biol 2000; 10:857–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Sánchez-Mejorada G, Rosales C. Signal transduction by immunoglobulin Fc receptors. J Leukoc Biol 1998; 63:521–533.PubMedGoogle Scholar
  10. 10.
    Monteiro R, Van De Winkel J. IgA Fc receptors. Annu Rev Immunol 2003; 21:177–204.PubMedCrossRefGoogle Scholar
  11. 11.
    Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol 2001; 19:275–290.PubMedCrossRefGoogle Scholar
  12. 12.
    Tridandapani S, Siefker K, Teillaud JL et al. Regulated expression and inhibitory function of FcgRIIb in human monocytic cells. J Biol Chem 2002; 277:5082–5089.PubMedCrossRefGoogle Scholar
  13. 13.
    Dib K, Andersson T. BETA 2 integrin signaling in leukocytes. Font Biosci 2000; 5:438–51.CrossRefGoogle Scholar
  14. 14.
    Takizawa F, Tsuji S, Nagasawa S. Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett 1996; 397:269–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Ofek I, Goldhar J, Keisari Y et al. Nonopsonic phagocytosis of microorganisms. Annu Rev Microbiol 1995; 49:239–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Lowell CA, Berton G. Integrin signal transduction in myeloid leukocytes. J Leukoc Biol 1999; 65:313–20.PubMedGoogle Scholar
  17. 17.
    Ehlers MR. CR3: A general purpose adhesion-recognition receptor essential for innate immunity. Microbes Infect 2000; 2:289–94.PubMedCrossRefGoogle Scholar
  18. 18.
    Ross GD, Vetvicka V. CR3 (CD11b, CD18): A phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. Clin Exp Immunol 1993; 92:181–4.PubMedGoogle Scholar
  19. 19.
    Ross GD, Cain JA, Myones BL et al. Specificity of membrane complement receptor type three (CR3) for beta-glucans. Complement 1987; 4:61–74.PubMedGoogle Scholar
  20. 20.
    Thornton BP, Vetvicka V, Pitman M et al. Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol 1996; 156:1235–46.PubMedGoogle Scholar
  21. 21.
    Diamond MS, Garcia-Aguilar J, Bickford JK et al. The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol 1993; 120:1031–43.PubMedCrossRefGoogle Scholar
  22. 22.
    Elward K, Gasque P. “Eat me” and “don’t eat me” signals govern the innate immune response and tissue repair in the CNS: Emphasis on the critical role of the complement system. Mol Immunol 2003; 40:85–94.PubMedCrossRefGoogle Scholar
  23. 23.
    Platt N, da Silva RP, Gordon S. Recognizing death: The phagocytosis of apoptotic cells. Trends Cell Biol 1998; 8:365–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Kagan VE, Borisenko GG, Serinkan BF et al. Appetizing rancidity of apoptotic cells for macrophages: Oxidation, externalization, and recognition of phosphatidylserine. Am J Physiol Lung Cell Mol Physiol 2003; 285:L1–17.PubMedGoogle Scholar
  25. 25.
    Fadok VA, Bratton DL, Frasch SC et al. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death Differ 1998; 5:551–62.PubMedCrossRefGoogle Scholar
  26. 26.
    Krieser RJ, White K. Engulfment mechanism of apoptotic cells. Curr Opin Cell Biol 2002; 14:734–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Fadok VA, Savill JS, Haslett C et al. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol 1992; 149:4029–35.PubMedGoogle Scholar
  28. 28.
    Hisatomi T, Sakamoto T, Sonoda KH et al. Clearance of apoptotic photoreceptors: Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin alphavbeta3. Am J Pathol 2003; 162:1869–79.PubMedGoogle Scholar
  29. 29.
    Stern M, Savill J, Haslett C. Human monocyte-derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis. Mediation by alpha v beta 3/CD36/thrombospondin recognition mechanism and lack of phlogistic response. Am J Pathol 1996; 149:911–21.PubMedGoogle Scholar
  30. 30.
    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 (alpha v beta 3). J Immunol 1998; 161:6250–7.PubMedGoogle Scholar
  31. 31.
    Moodley Y, Rigby P, Bundell C et al. Macrophage recognition and phagocytosis of apoptotic fibroblasts is critically dependent on fibroblast-derived thrombospondin 1 and CD36. Am J Pathol 2003; 162:771–9.PubMedGoogle Scholar
  32. 32.
    Albert ML, Kim JI, Birge RB. Alphavbeta5 integrin recruits the CrkII-Dockl80-racl complex for phagocytosis of apoptotic cells. Nat Cell Biol 2000; 2:899–905.PubMedCrossRefGoogle Scholar
  33. 33.
    Finnemann SC, Silverstein RL. Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J Exp Med 2001; 194:1289–98.PubMedCrossRefGoogle Scholar
  34. 34.
    Hoffmann PR, deCathelineau AM, Ogden CA et al. Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol 2001; 155:649–59.PubMedCrossRefGoogle Scholar
  35. 35.
    Hughes J, Liu Y, Van Damme J et al. Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: Mediation by a novel CD36-independent vitronectin receptor/thrombospondin recognition mechanism that is uncoupled from chemokine secretion. J Immunol 1997; 158:4389–97.PubMedGoogle Scholar
  36. 36.
    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; 274:5901–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Kawasaki Y, Nakagawa A, Nagaosa K et al. Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells. J Biol Chem 2002; 277:27559–66.PubMedCrossRefGoogle Scholar
  38. 38.
    Imachi H, Murao K, Hiramine C et al. Human scavenger receptor Bl is involved in recognition of apoptotic thymocytes by thymic nurse cells. Lab Invest 2000; 80:263–70.PubMedCrossRefGoogle Scholar
  39. 39.
    Platt N, da Silva RP, Gordon S. Class A scavenger receptors and the phagocytosis of apoptotic cells. Immunol Lett 1999; 65:15–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Tait JF, Smith C. Phosphatidylserine receptors: Role of CD36 in binding of anionic phospholipid vesicles to monocytic cells. J Biol Chem 1999; 274:3048–54.PubMedCrossRefGoogle Scholar
  41. 41.
    Ryeom SW, Silverstein RL, Scotto A et al. Binding of anionic phospholipids to retinal pigment epithelium may be mediated by the scavenger receptor CD36. J Biol Chem 1996; 271:20536–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Savill J, Hogg N, Ren Y et al. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 1992; 90:1513–22.PubMedCrossRefGoogle Scholar
  43. 43.
    Lemke G, Lu Q. Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol 2003; 15:31–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Hall MO, Prieto AL, Obin MS et al. Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res 2001; 73:509–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Hall MO, Obin MS, Prieto AL et al. Gas6 binding to photoreceptor outer segments requires gamma-carboxyglutamic acid (Gla) and Ca(2+) and is required for OS phagocytosis by RPE cells in vitro. Exp Eye Res 2002; 75:391–400.PubMedCrossRefGoogle Scholar
  46. 46.
    Scott RS, McMahon EJ, Pop SM et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 2001; 411:207–11.PubMedCrossRefGoogle Scholar
  47. 47.
    Ogden CA, deCathelineau A, Hoffmann PR et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001; 194:781–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Vandivier RW, Ogden CA, Fadok VA et al. Role of surfactant proteins A, D, and Clq in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002; 169:3978–86.PubMedGoogle Scholar
  49. 49.
    Strzelecka A, Kwiatkowska K, Sobota A. Tyrosine phosphorylation and Fcg receptor-mediated phagocytosis. FEBS Letters 1997; 400:11–14.PubMedCrossRefGoogle Scholar
  50. 50.
    Korade-Mirnics Z, Corey SJ. Src kinase-mediated signaling in leukocytes. J Leukoc Biol 2000; 68:603–613.PubMedGoogle Scholar
  51. 51.
    Turner MES, Colucci F, Di Santo JP et al. Tyrosine kinase SYK: Essential functions for immunoreceptor signalling. Immunol Today 2000; 21:148–154.PubMedCrossRefGoogle Scholar
  52. 52.
    Allen LA, Aderem A. Molecular definition of distinct cytoskeletal structures involved in complement-and Fc receptor-mediated phagocytosis in macrophages. J Exp Med 1996; 184:627–37.PubMedCrossRefGoogle Scholar
  53. 53.
    Kiefer F, Brumell J, Al Alawi N et al. The Syk protein tyrosine kinase is essential for Fcgamma receptor signaling in macrophages and neutrophils. Mol Cell Biol 1998; 18:4209–20.PubMedGoogle Scholar
  54. 54.
    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; 66:4541–4.PubMedGoogle Scholar
  55. 55.
    Hu B, Punturieri A, Todt J et al. Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events. J Leukoc Biol 2002; 71:881–9.PubMedGoogle Scholar
  56. 56.
    Moore KJ, El Khoury J, Medeiros LA et al. A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem 2002; 277:47373–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Huang MM, Bolen JB, Barnwell JW et al. Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. Proc Natl Acad Sci USA 1991; 88:7844–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Su HP, Nakada-Tsukui K, Tosello-Trampont AC 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; 277:11772–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Patel M, Morrow J, Maxfield F et al. The cytoplasmic domain of LDL receptor-related protein, but not that of the LDL receptor, triggers phagocytosis. J Biol Chem 2003, (Epub ahead of print Aug. 26 2003).Google Scholar
  60. 60.
    Garcia-Garcia E, Rosales C. Signal transduction during Fc receptor-mediated phagocytosis. J Leukoc Biol 2002; 72:1092–108.PubMedGoogle Scholar
  61. 61.
    Raeder EM, Mansfield PJ, Hinkovska-Galcheva V et al. Syk activation initiates downstream signaling events during human polymorphonuclear leukocyte phagocytosis. J Immunol 1999; 163:6785–6793.PubMedGoogle Scholar
  62. 62.
    Yamamori T, Inanami O, Nagahata H et al. Roles of p38MAPK, PKC and PI3-K in the signaling pathways of NADPH oxidase activation and phagocytosis in bovine polymorphonuclear leukocytes. FEBS Lett 2000; 467:253–258.PubMedCrossRefGoogle Scholar
  63. 63.
    Cox D, Tseng CC, Bjekic G et al. A requirement for phosphatidylinositol 3-kinase in pseudopod extension. J Biol Chem 1999; 274:1240–1247.PubMedCrossRefGoogle Scholar
  64. 64.
    Garcia-Garcia E, Rosales R, Rosales C. Phosphatidylinositol 3-kinase and extracellular signal-regulated kinase are recruited for Fc receptor-mediated phagocytosis during monocyte to macrophage differentiation. Journal of Leukocyte Biology 2002; 72:107–114.PubMedGoogle Scholar
  65. 65.
    Ninoyima N, Hazeki K, Fukui Y et al. Involvement of phosphatidylinositol 3-kinase in Fcg receptor signaling. J Biol Chem 1994; 269:22732–22737.Google Scholar
  66. 66.
    Booth JW, Trimble WS, Grinstein S. Membrane dynamics in phagocytosis. Semin Immunol 2001; 13:357–364.PubMedCrossRefGoogle Scholar
  67. 67.
    May RC, Machesky LM. Phagocytosis and the actin cytoskeleton. J Cell Sci 2001; 114:1061–1077.PubMedGoogle Scholar
  68. 68.
    Gillooly DJ, Simonsen A, Stenmark H. Phosphoinositides and phagocytosis. J Cell Biol 2001; 155:15–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Coxon PY, Rane MJ, Powell DW et al. Differential mitogen-activated protein kinase stimulation by Fcg receptor IIa and Fcg receptor IIIb determines the activation phenotype of human neutrophils. J Immunol 2000; 164:6530–6537.PubMedGoogle Scholar
  70. 70.
    Wymann MP, Sozzani S, Altruda F et al. Lipids on the move: Phosphoinositide 3-kinases in leukocyte function. Immunol Today 2000; 21:260–264.PubMedCrossRefGoogle Scholar
  71. 71.
    Cox D, Dale BM, Kashiwada M et al. A regulatory role for Src homology 2 domain-containing inositol 5′-phosphatase (SHIP) in phagocytosis mediated by Fcg receptors and complement receptor 3 (aMb2; CD11b/CD18). J Exp Med 2001; 193:61–72.PubMedCrossRefGoogle Scholar
  72. 72.
    Lutz MA, Correll PH. Activation of CR3-mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase C zeta. J Leukoc Biol 2003; 73:802–14.PubMedCrossRefGoogle Scholar
  73. 73.
    Gagnon E, Duclos S, Rondeau C et al. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 2002; 110:119–31.PubMedCrossRefGoogle Scholar
  74. 74.
    Houde M, Bertholet S, Gagnon E et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 2003; 425:402–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Leverrier Y, Ridley AJ. Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages. Curr Biol 2001; 11:195–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Leverrier Y, Okkenhaug K, Sawyer C et al. Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages. J Biol Chem 2003; 278:38437–42.PubMedCrossRefGoogle Scholar
  77. 77.
    Dempsey EC, Newton AC, Mochly-Rosen D et al. Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol 2000; 279:L429–L438.PubMedGoogle Scholar
  78. 78.
    Raeder EM, Mansfield PJ, Hinkovska-Galcheva V et al. Sphingosine blocks human polymorphonuclear leukocyte phagocytosis through inhibition of mitogen-activated protein kinase activation. Blood 1999; 93:686–693.PubMedGoogle Scholar
  79. 79.
    Karimi K, Gemmill TR, Lennartz MR. Protein kinase C and a calcium-independent phospholipase are required for IgG-mediated phagocytosis by Mono-Mac-6 cells. J Leukoc Biol 1999; 65:854–862.PubMedGoogle Scholar
  80. 80.
    Breton A, Descoteaux A. Protein kinase C-a participates in FcgR-mediated phagocytosis in macrophages. Biochem Biophys Res Com 2000; 276:472–476.PubMedCrossRefGoogle Scholar
  81. 81.
    Dekker LV, Leitges M, Altschuler G et al. Protein kinase C-b contributes to NADPH oxidase activation in neutrophils. Biochem J 2000; 347:285–289.PubMedCrossRefGoogle Scholar
  82. 82.
    Melendez AJ, Harnett MM, Allen JM. FcgRI activation of phospholipase Cgl and protein kinase C in dibutyryl cAMP-differentiated U937 cells is dependent solely on the tyrosine-kinase activated form of phosphatidylinositol 3-kinase. Immunol 1999; 98:1–8.CrossRefGoogle Scholar
  83. 83.
    Brumell JH, Howard JC, Craig K et al. Expression of the protein kinase C substrate pleckstrin in macrophages: Association with phagosomal membranes. J Immunol 1999; 163:3388–3395.PubMedGoogle Scholar
  84. 84.
    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; 165:2809–2817.PubMedGoogle Scholar
  85. 85.
    Karimi K, Lennartz MR. Mitogen-activated protein kinase is activated during IgG-mediated phagocytosis, but it is not required for target ingestion. Inflammation 1998; 22:67–82.PubMedCrossRefGoogle Scholar
  86. 86.
    Lennartz MR, Yuen AFC, McKenzie Masi S et al. Phospholipase A2 inhibition results in sequestration of plasma membrane into electronlucent vesicles during IgG-mediated phagocytosis. J Cell Sci 1997; 110:2041–2052.PubMedGoogle Scholar
  87. 87.
    Fallman M, Gullberg M, Hellberg C et al. Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidylcholine-derived diglyceride in human neutrophils. Involvement of phospholipase D and direct evidence for a positive feedback signal of protein kinase. J Biol Chem 1992; 267:2656–63.PubMedGoogle Scholar
  88. 88.
    Sergeant S, McPhail LC. Opsonized zymosan stimulates the redistribution of protein kinase C isoforms in human neutrophils. J Immunol 1997; 159:2877–85.PubMedGoogle Scholar
  89. 89.
    Akiba S, Mizunaga S, Kume K et al. Involvement of group VI Ca2+-independent phospholipase A2 in protein kinase C-dependent arachidonic acid liberation in zymosan-stimulated macrophage-like P388D1 cells. J Biol Chem 1999; 274:19906–19912.PubMedCrossRefGoogle Scholar
  90. 90.
    Mehta D, Rahman A, Malik AB. Protein kinase C-alpha signals rho-guanine nucleotide dissociation inhibitor phosphorylation and rho activation and regulates the endothelial cell barrier function. J Biol Chem 2001; 276:22614–20.PubMedCrossRefGoogle Scholar
  91. 91.
    Caron E, Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 1998; 282:1717–21.PubMedCrossRefGoogle Scholar
  92. 92.
    Todt JC, Hu B, Punturieri A et al. Activation of protein kinase C beta II by the stereo-specific phosphatidylserine receptor is required for phagocytosis of apoptotic thymocytes by resident murine tissue macrophages. J Biol Chem 2002; 277:35906–14.PubMedCrossRefGoogle Scholar
  93. 93.
    Lennartz MR. Phospholipases and phagocytosis: The role of phospholipid-derived second messengers in phagocytosis. Int J Biochem Cell Biol 1999; 31:415–430.PubMedCrossRefGoogle Scholar
  94. 94.
    Lennartz MR, Brown EJ. Arachidonic acid is essential for IgG Fc receptor-mediated phagocytosis by human monocytes. J Immunol 1991; 147:621–626.PubMedGoogle Scholar
  95. 95.
    Lennartz MR, Lefkowith JB, Bromley FA et al. Immunoglobulin G-mediated phagocytosis activates a calcium-independent, phosphatidylethanolamine-specific phospholipase. J Leukoc Biol 1993; 54:389–398.PubMedGoogle Scholar
  96. 96.
    Karimi K, Lennartz MR. Protein kinase C activation precedes arachidonic acid release during IgG-mediated phagocytosis. J Immunol 1995; 155:5786–5794.PubMedGoogle Scholar
  97. 97.
    Pollaud-Cherion C, Vandaele J, Quartulli F et al. Involvement of calcium and arachidonate metabolism in acetylated-low-density-lipoprotein-stimulated tumor-necrosis-factor-alpha production by rat peritoneal macrophages. Eur J Biochem 1998; 253:345–53.PubMedCrossRefGoogle Scholar
  98. 98.
    Bhattacharya S, Patel R, Sen N et al. Dual signaling by the alpha(v)beta(3)-integrin activates cytosolic PLA(2) in bovine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 2001; 280:L1049–56.PubMedGoogle Scholar
  99. 99.
    Azzoni L, Kamoun M, Salcedo TW et al. Stimulation of FcgRIIIA results in phospholipase C-g1 tyrosine phosphorylation and p56lck activation. J Exp Med 1992; 176:1745–1750.PubMedCrossRefGoogle Scholar
  100. 100.
    Shen Z, Lin C-T, Unkeless JC. Correlation among tyrosine phosphorylation of Sch, p72syk, PLC-g1, and [Ca2+]i flux in FcgRIIA signaling. J Immunol 1994; 152:3017–3023.PubMedGoogle Scholar
  101. 101.
    Botelho RJ, Teruel M, Dierckman R et al. Localized biphasic changes in phosphatidylinositol-4,5-biphosphate at sites of phagocytosis. J Cell Biol 2000; 151:1353–1368.PubMedCrossRefGoogle Scholar
  102. 102.
    Serrander L, Fallman M, Stendahl O. Activation of phospholipase D is an early event in integrin-mediated signalling leading to phagocytosis in human neutrophils. Inflammation 1996; 20:439–50.PubMedCrossRefGoogle Scholar
  103. 103.
    Kusner DJ, Hall CF, Schlesinger LS. Activation of phospholipase D is tighdy coupled to the phagocytosis of Mycobacterium tuberculosis or opsonized zymosan by human macrophages. J Exp Med 1996; 184:585–95.PubMedCrossRefGoogle Scholar
  104. 104.
    Nakamura I, Lipfert L, Rodan GA et al. Convergence of alpha(v)beta(3) integrin-and macrophage colony stimulating factor-mediated signals on phospholipase Cgamma in prefusion osteoclasts. J Cell Biol 2001; 152:361–73.PubMedCrossRefGoogle Scholar
  105. 105.
    Suchard SJ, Mansfield PJ, Boxer LA et al. Mitogen-activated protein kinase action during IgG-dependent phagocytosis in human neutrophils. Inhibition by Ceramide. J Immunol 1997; 158:4961–4967.PubMedGoogle Scholar
  106. 106.
    Fallman M, Andersson R, Andersson T. Signaling properties of CR3 (CD11b/CD18) and CR1 (CD35) in relation to phagocytosis of complement-opsonized particles. J Immunol 1993; 151:330–8.PubMedGoogle Scholar
  107. 107.
    Widmann C, Gibson S, Jarpe MB et al. Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiol Rev 1999; 79:143–80.PubMedGoogle Scholar
  108. 108.
    Mansfield PJ, Shayman JA, Boxer LA. Regulation of polymorphonudear leukocyte phagocytosis by myosin light chain kinase after activation of mitogen-activated protein kinase. Blood 2000; 95:2407–2412.PubMedGoogle Scholar
  109. 109.
    Kalhammer G, Bähler M. Unconventional myosins. Essays Biochem 2000; 35:33–42.PubMedGoogle Scholar
  110. 110.
    Reddy SM, Hsiao KH, Abernethy VE 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; 169:702–13.PubMedGoogle Scholar
  111. 111.
    Kurosaka K, Takahashi M, Kobayashi Y. Activation of extracellular signal-regulated kinase 1/2 is involved in production of CXC-chemokine by macrophages during phagocytosis of late apoptotic cells. Biochem Biophys Res Commun 2003; 306:1070–4.PubMedCrossRefGoogle Scholar
  112. 112.
    Kurosaka K, Watanabe N, Kobayashi Y. Production of proinflammatory cytokines by resident tissue macrophages after phagocytosis of apoptotic cells. Cell Immunol 2001; 211:1–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Castellano F, Chavrier P, Caron E. Actin dynamics during phagocytosis. Semin Immunol 2001; 13:347–55.PubMedCrossRefGoogle Scholar
  114. 114.
    Wittmann T, Waterman-Storer CM. Cell motility: Can Rho GTPases and microtubules point the way? J Cell Sci 2001; 114:3795–803.PubMedGoogle Scholar
  115. 115.
    Swanson J, Baer S. Phagocytosis by zippers and triggers. Trends Cell Biol 1995; 5:89–93.PubMedCrossRefGoogle Scholar
  116. 116.
    Newman SL, Mikus LK, Tucci MA. Differential requirements for cellular cytoskeleton in human macrophage complement receptor-and Fc receptor-mediated phagocytosis. J Immunol 1991; 146:967–74.PubMedGoogle Scholar
  117. 117.
    Welch MD, Mullins RD. Cellular control of actin nucleation. Annu Rev Cell Dev Biol 2002; 18:247–88.PubMedCrossRefGoogle Scholar
  118. 118.
    Turner M, Billadeau D. VAV proteins as signal integrators for multi-subunit immune-recognition receptors. Nat Rev Immunol 2002; 7:476–86.CrossRefGoogle Scholar
  119. 119.
    Dib K, Melander F, Andersson T. Role of pl90RhoGAP in beta 2 integrin regulation of RhoA in human neutrophils. J Immunol 2001; 166:6311–22.PubMedGoogle Scholar
  120. 120.
    Patel JC, Hall A, Caron E. Vav regulates activation of Rac but not Cdc42 during FcgammaR-mediated phagocytosis. Mol Biol Cell 2002; 13:1215–26.PubMedCrossRefGoogle Scholar
  121. 121.
    Coppolino MG, Krause M, Hagendorff P et al. Evidence for a molecular complex consisting of Fyb/ SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. J Cell Sci 2001; 114:4307–18.PubMedGoogle Scholar
  122. 122.
    Zhou X, Li J, Kucik DF. The microtubule cytoskeleton participates in control of beta2 integrin avidity. J Biol Chem 2001; 276:44762–9.PubMedCrossRefGoogle Scholar
  123. 123.
    Gumienny TL, Brugnera E, Tosello-Trampont AC et al. CED-12/ELMO, a novel member of the CrkII/Dockl80/Rac pathway, is required for phagocytosis and cell migration. Cell 2001; 107:27–41.PubMedCrossRefGoogle Scholar
  124. 124.
    Le Cabec V, Carreno S, Moisand A et al. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J Immunol 2002; 169:2003–9.PubMedGoogle Scholar
  125. 125.
    Tosello-Trampont A, Nakada-Tsukui K, KS R. Engulfment of apoptotic cells is negatively regulated by Rho-mediated signaling. 2003, (Epub ahead of print Sep 26).Google Scholar
  126. 126.
    May RC, Caron E, Hall A et al. Involvement of the Arp2/3 complex in phagocytosis mediated by FcgR or CR3. Nature Cell Biology 2000; 2:246–248.PubMedCrossRefGoogle Scholar
  127. 127.
    Olazabal IM, Caron E, May RC et al. Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcgammaR, phagocytosis. Curr Biol 2002; 12:1413–18.PubMedCrossRefGoogle Scholar
  128. 128.
    Lorenzi R, Brickell PM, Katz DR et al. Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis. Blood 2000; 95:2943–6.PubMedGoogle Scholar
  129. 129.
    Leverrier Y, Lorenzi R, Blundell MP et al. Cutting edge: The Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells. J Immunol 2001; 166:4831–4.PubMedGoogle Scholar
  130. 130.
    Allen LA, Aderem A. A role for MARCKS, the alpha isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages. J Exp Med 1995; 182:829–840.PubMedCrossRefGoogle Scholar
  131. 131.
    Scott MP, Zappacosta F, Kim EY et al. Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1. J Biol Chem 2002; 277:28238–46.PubMedCrossRefGoogle Scholar
  132. 132.
    Swanson JA, Johnson MT, Beningo K et al. A contractile activity that closes phagosomes in macrophages. J Cell Sci 1999; 112:307–316.PubMedGoogle Scholar
  133. 133.
    Araki N, Hatae T, Furukawa A et al. Phosphoinositide-3-kinase-independent contractile activities associated with Fcgamma-receptor-mediated phagocytosis and macropinocytosis in macrophages. J Cell Sci 2003; 116:247–57.PubMedCrossRefGoogle Scholar

Copyright information

© and Springer Science+Business Media 2005

Authors and Affiliations

  • Erick García-García
    • 1
  1. 1.Immunology Department, Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoMexico CityMexico

Personalised recommendations