Calcium Signaling during Phagocytosis

  • Alirio J. Melendez
Part of the Medical Intelligence Unit book series (MIUN)


Phagocytosis is important for a wide diversity of organisms. From simple unicellular organisms that use phagocytosis to eat, to complex metazoans in which phagocytic cells represent an essential branch of the immune system. Evolution has armed cells with a fantastic repertoire of molecules that serve to bring about this complex event regardless of the organism or specific molecules concerned. However, all phagocytic processes are driven by a finely controlled rearrangement of the actin cytoskeleton where calcium (Ca2+) signals play important roles. Ca2+ plays many roles in cytoskeletal changes by affecting the actions of a number of contractile proteins, as well as being a cofactor for the activation of a number of intracellular signaling proteins, known to play important roles during phagocytosis. In the mammalian immune system, the requirement of Ca2+ for the initial steps in phagocytosis, and the subsequent phagosome maturation, can be quite different depending on the type of cell and on the type of receptor that is driving phagocytosis.


Human Neutrophil Complement Receptor Internal Store Sphingosine Kinase Intracellular Free Calcium 
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  1. 1.
    Metchnikoff E. Sur la lutte des cellules de l’organisme contre l’invasion des microbes. Ann Inst Pasteur 1887; 1:321–345.Google Scholar
  2. 2.
    Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999; 17:593–623.PubMedGoogle Scholar
  3. 3.
    Cardelli J. Phagocytosis and micropinocytosis in Dictyostelium: Phosphoinositidebased processes, biochemically distinct. Traffick 2001; 2:311–320.Google Scholar
  4. 4.
    Franc NC, White K, Ezekowitz RA. Phagocytosis and development: Back to the future. Curr Opin Immunol 1999; 11:47–52.PubMedGoogle Scholar
  5. 5.
    Tan Z, Boss WF. Association of phosphatidylinositol kinase, phosphatidylinositol monophosphate kinase, and diacylglycerol kinase with the cytoskeleton and F-actin fractions of carrot (Daucus carota L.) cells grown in suspension culture. Plant Physiol 1992; 100:2116–2120.PubMedGoogle Scholar
  6. 6.
    Yamamoto K, Pardee JD, Reidler J et al. Mechanism of interaction of Dictyostelium severin with actin filaments. J Cell Biol 1982; 95:711–719.PubMedGoogle Scholar
  7. 7.
    Witke W, Hofmann A, Koppel B et al. The Ca2+-binding domains in nonmuscle type alpha-actinin: Biochemical and genetic analysis. J Cell Biol 1993; 121:599–606.PubMedGoogle Scholar
  8. 8.
    Fechheimer M, Taylor DL. Isolation and characterization of a 30,000-dalton calcium-sensitive actin cross-linking protein from Dictyostelium discoideum. J Biol Chem 1984; 259:4514–4520.PubMedGoogle Scholar
  9. 9.
    Doring V, Veretout F, Albrecht R et al. The in vivo role of annexin VII (synexin)-characterization of an annexin VII deficient Dictyostelium mutant indicates an involvement in calcium-regulated processes. J Cell Sci 1995; 108:2065–2076.PubMedGoogle Scholar
  10. 10.
    Zhu Q, Liu T, Clarke M. Calmodulin and the contractile vacuole complex in mitotic cells of Dictyostelium discoideum. J Cell Sci 1993; 104:1119–1127.PubMedGoogle Scholar
  11. 11.
    Dharamsi A, Tessarolo D, Coukell B et al. CBP1 associates with the Dictyostelium cytoskeleton and is important for normal cell aggregation under certain developmental conditions. Exp Cell Res 2000; 258:298–309.PubMedGoogle Scholar
  12. 12.
    Huttenlocher A, Palecek SP, Lu Q et al. Regulation of cell migration by the calcium-dependent protease calpain. J Biol Chem 1997; 272:32719–32722.PubMedGoogle Scholar
  13. 13.
    Rabinovitch M. Professional and nonprofessional phagocytes: An introduction. Trends Cell Biol 1995; 5:85–87.PubMedGoogle Scholar
  14. 14.
    Kwiatkowska K, Sobota A. Signaling pathways in phagocytosis. BioEssays 1999; 21:422–431.PubMedGoogle Scholar
  15. 15.
    Indik ZK, Park JG, Hunter S et al. The molecular dissection of Fcγ receptor mediated phagocytosis. Blood 1995; 86:4389–4399.PubMedGoogle Scholar
  16. 16.
    Hampton MB, Kettle AJ, Winterbourn CC. Inside the neutrophil phagosome: Oxidants, myeloperoxidase, and bacterial killing. Blood 1998; 92:3007–3017.PubMedGoogle Scholar
  17. 17.
    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; 191:287–302.PubMedGoogle Scholar
  18. 18.
    Ofek I, Goldhar J, Keisari Y et al. Nonopsonic phagocytosis of microorganisms. Annu Rev Microbiol 1995; 49:239–276.PubMedGoogle Scholar
  19. 19.
    Schutt C. Fighting infection: The role of lipopolysaccharide binding proteins CD14 and LBP. Pathobiology 1999; 67:227–229.PubMedGoogle Scholar
  20. 20.
    In: Roitt IM, ed. The basis of immunology. Essential Immunology. Oxford: Blackwell Scientific, 1994.Google Scholar
  21. 21.
    van Egmond MH, Hanneke van Vuuren AJ, van de Winkel JG. The human Fc receptor for IgA (FcαRI, CD89) on transgenic peritoneal macrophages triggers phagocytosis and tumor cell lysis. Immunol Lett 1999; 68:83–87.PubMedGoogle Scholar
  22. 22.
    Yokota A, Yukawa K, Yamamoto A et al. Two forms of the low affinity Fc receptor for IgE differentially mediate endocytosis and phagocytosis: Identification of the critical cytoplasmic domains. Proc Nat Acad Sci USA 1992; 89:5030–5034.PubMedGoogle Scholar
  23. 23.
    Sanchez-Mejorada G, Rosales C. Signal transduction by immunoglobulin Fc receptors. J Leuk Biol 1998; 63:521–533.Google Scholar
  24. 24.
    Indik ZK, Hunter S, Huang MM et al. The high affinity Fc gamma receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: The gamma subunit of Fc gamma RIIIA imparts phagocytic function to Fc gamma RI. Exp Hematol 1994; 22:599–606.PubMedGoogle Scholar
  25. 25.
    Tuijnman WB, Capel PJ, van de Winkel JG. Human low affinity IgG receptor Fc gamma Rlla (CD32) introduced into mouse fibroblasts mediates phagocytosis of sensitized erythrocytes. Blood 1992; 79:1651–1656.PubMedGoogle Scholar
  26. 26.
    Park JG, Isaacs RE, Chien P et al. In the absence of other Fc receptors, Fc gamma RIIIA transmits a phagocytic signal that requires the cytoplasmic domain of its gamma subunit. J Clin Invest 1993; 92:1967–1973.PubMedGoogle Scholar
  27. 27.
    Indik ZK, Pan XQ, Huang MM et al. Insertion of cytoplasmic tyrosine sequences into the nonphagocytic receptor Fc gamma RIIB establishes phagocytic function. Blood 1994; 83:2072–2080.PubMedGoogle Scholar
  28. 28.
    Kimberly RP, Ahlstrom JW, Click ME et al. The glycosyl phosphatidylinositol-linked Fc gamma RIIIPMN mediates transmembrane signaling events distinct from Fc gamma RII. J Exp Med 1990; 171:1239–1255.PubMedGoogle Scholar
  29. 29.
    Salmon JE, Brogle EJ, Edberg JC et al. Fcgamma receptor III induces actin polymerization in human neutrophils and primes phagocytosis mediated by Fcgamma receptor II. J Immunol 1991; 146:997–1004.PubMedGoogle Scholar
  30. 30.
    Chuang FY, Sassaroli M, Unkeless JC. Convergence of Fc-gamma receptor IIA and Fc gamma receptor IIIB signaling pathways in human neutrophils. J Immunol 2000; 164:350–360.PubMedGoogle Scholar
  31. 31.
    Garcia-Garcia E, Rosales C. Signal transduction during Fc receptor-mediated phagocytosis. J Leuk Biol 2002; 72:1092–1108.Google Scholar
  32. 32.
    Smith LC, Azumi K, Nonaka M. Complement systems in invertebrates. The ancient alternative and lectin pathways. Immunopharmacology 1999; 42:107–120.PubMedGoogle Scholar
  33. 33.
    Ravetch JV, Clynes RA. Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 1998; 16:421–432.PubMedGoogle Scholar
  34. 34.
    Brown EJ. Complement receptors and phagocytosis. Curr Opin Immunol 1991; 3:76–82.PubMedGoogle Scholar
  35. 35.
    Diamond MS, Garcia-Aguilar J, Bickford J 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; 120:1031–1043.PubMedGoogle Scholar
  36. 36.
    Brown EJ. The role of extracellular matrix proteins in the control of phagocytosis. J Leuk Biol 1986; 39:579–591.Google Scholar
  37. 37.
    Pommier CG, Inada S, Fries LF et al. Plasma fibronectin enhances phagocytosis of opsonized particles by human peripheral blood monocytes. J Exp Med 1983; 157:1844–1854.PubMedGoogle Scholar
  38. 38.
    Oxvig C, Lu C, Springer TA. Conformational changes in tertiary structure near the ligand binding site of an integrin I domain. Proc Nat Acad Sci USA 1999; 96:2215–2220.PubMedGoogle Scholar
  39. 39.
    Chatila TA, Geha RS, Arnaout MA. Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules. J Cell Biol 1989; 109:3435–3444.PubMedGoogle Scholar
  40. 40.
    Detmers PA, Wright SD, Olsen E et al. Aggregation of complement receptors on human neutronphils in the absence of ligand. J Cell Biol 1987; 105:1137–1145.PubMedGoogle Scholar
  41. 41.
    Allen LA, Aderem A. Mechanisms of phagocytosis. Curr Opin Immunol 1996; 8:36–40.PubMedGoogle Scholar
  42. 42.
    Blystone SD, Graham IL, Lindberg FP et al. Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1. J Cell Biol 1994; 127:1129–1137.PubMedGoogle Scholar
  43. 43.
    Stahl PD, Ezekowitz RA. The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol 1998; 10:50–55.PubMedGoogle Scholar
  44. 44.
    Devitt A, Moffatt OD, Raykundalia C et al. Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 1998; 392:505–509.PubMedGoogle Scholar
  45. 45.
    Platt N, da Silva RP, Gordon S. Recognizing death: The phagocytosis of apoptotic cells. Trends Cell Biol 1998; 8:365–372.PubMedGoogle Scholar
  46. 46.
    Parnaik R, Raff MC, Scholes J. Differences between the clearance of apoptotic cells by professional and nonprofessional phagocytes. Curr Biol 2000; 10:857–860.PubMedGoogle Scholar
  47. 47.
    Meagher LC, Savill JS, Baker A et al. Phagocytosis of apoptotic neutrophils does not induce macrophage release of thromboxane B2. J Leuk Biol 1992; 52:269–273.Google Scholar
  48. 48.
    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-beta, PGE2, and PAF. J Clin Invest 1998; 101:890–898.PubMedGoogle Scholar
  49. 49.
    Voll RE, Herrmann M, Roth EA et al. Immunosuppressive effects of apoptotic cells. Nature 1997; 390:350–351.PubMedGoogle Scholar
  50. 50.
    Savill J. Apoptosis. Phagocytic docking without shocking. Nature 1998; 392:442–443.PubMedGoogle Scholar
  51. 51.
    Fadok VA, Bratton DL, Rose DM et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 2000; 405:85–90.PubMedGoogle Scholar
  52. 52.
    Chung S, Gumienny TL, Hengartner MO et al. A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nature Cell Biol 2000; 2:931–937.PubMedGoogle Scholar
  53. 53.
    Roubey RA, Ross GD, Merrill JT et al. Staurosporine inhibits neutrophil phagocytosis but not iC3b binding mediated by CR3 (CD11b/CD18). J Immunol 1991; 146:3557–3562.PubMedGoogle Scholar
  54. 54.
    Zhou Z, Hartwleg E, Horvitz HR. CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 2001; 104:43–56.PubMedGoogle Scholar
  55. 55.
    Kaplan G. Differences in the mode of phagocytosis with Fc and C3 receptors in macrophages. Scand J Immunol 1977; 6:797–807.PubMedGoogle Scholar
  56. 56.
    Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000; 1:11–21.PubMedGoogle Scholar
  57. 57.
    Bootman MD, Berridge MJ, Roderick HL. Calcium signalling: More messengers, more channels, more complexity. Curr Biol 2002; 12:R563–R565.PubMedGoogle Scholar
  58. 58.
    Bootman MD, Lipp P, Berridge MJ. The organisation and functions of local Ca2+ signals. J Cell Sci 2001; 114:2213–2222.PubMedGoogle Scholar
  59. 59.
    Pryor PR, Mullock BM, Bright NA et al. The role of intraorganellar Ca2+ in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles. J Cell Biol 2000; 149:1053–1062.PubMedGoogle Scholar
  60. 60.
    Mao C, Kim SH, Almenoff JS et al. Molecular cloning and characterization of SCaMPER, a sphingoid Ca2+ release-mediating protein from endoplasmic reticulum. Proc Natl Acad Sci USA 1996; 93:1993–1996.PubMedGoogle Scholar
  61. 61.
    Schnurbus R, De Pietri Tnelli D, Grohovas F et al. Reevaluation of primary structure, topology and localization of SCaMPER, a putative intracellular Ca2+ channel activated by sphingpsylphosphocholine. Biochem J 2002; 362:183–189.PubMedGoogle Scholar
  62. 62.
    Berridge MD. Capacitative calcium entry. Biochem J 1995; 312:1–11.PubMedGoogle Scholar
  63. 63.
    Cancela JM, van Coppenolle F, Galione A et al. Transformation of local Ca2+ spikes to global Ca2+ transients: The combinatioral roles of multiple Ca2+ releasing messengers. EMBO J 2002; 21:909–919.PubMedGoogle Scholar
  64. 64.
    Mingen O, Thompson JL, Shuttleworth TJ. Reciprocal regulation of capacitative and arachidonate-regulated noncapacitative Ca2+ entry pathways. J Biol Chem 2001; 276:35676–35683.Google Scholar
  65. 65.
    Montell C. Physiology, phylogeny and functions of the TRP superfamily of cation channels. Science’s STKE 2001, http://stke.sciencemag.iorg/cgi/cx)ntent/full/OC_sigtrans, 2001/90/rel.Google Scholar
  66. 66.
    Yue LX, Peng JB, Hediger MA et al. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature 2001; 410:705–709.PubMedGoogle Scholar
  67. 67.
    Voets T, Prenen J, Fleig A et al. CaT1 and the calcium release-activated calcium channel manifest distinct pore properties. J Biol Chem 2001; 276:47767–47770.PubMedGoogle Scholar
  68. 68.
    Tapper H. The secretion of preformed granules by macrophages and neutrophils. J Leukocyte Biol 1996; 59:613–622.PubMedGoogle Scholar
  69. 69.
    Brumell JH, Volchuk A, Sengelov H et al. Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments. J Immunol 1995; 155:5750–5759.PubMedGoogle Scholar
  70. 70.
    Floto RA, Mahaut-Smith MP, Somasundaram B et al. IgG-induced Ca2+ oscillations in differentiated U937 cells; a study using laser scanning confocal microscopy and coloaded Fluo-3 and Fura-red fluorescent probes. Cell Calcium 1995; 18:377–389.PubMedGoogle Scholar
  71. 71.
    Mandeville JT, Maxfield FR. Calcium and signal transduction in granulocytes. Curr Opin Hematol 1996; 3:63–70.PubMedGoogle Scholar
  72. 72.
    Pryor PR, Mullock BM, Bright NA et al. The role of intraorganellar Ca2+ in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles. J Cell Biol 2000; 149:1053–1062.PubMedGoogle Scholar
  73. 73.
    Peters C, Mayer A. Ca2+/calmodulin signals the completion of docking and triggers a late step of vacuole fusion. Nature 1998; 396:575–580.PubMedGoogle Scholar
  74. 74.
    Lundqvist-Gustafsson H, Gustafsson M, Dahlgren C. Dynamic Ca2+ changes in neutrophil phagosomes. A source for intracellular Ca2+ during phagolysosome formation?. Cell Calcium 2000; 27:353–362.PubMedGoogle Scholar
  75. 75.
    Berridge MJ. Inositol trisphosphate and calcium signalling. Nature 1993; 361:315–325.PubMedGoogle Scholar
  76. 76.
    Rosales C, Brown EJ. Signal transduction by neutrophil immunoglobulin G Fc receptors: Dissociation of intracytoplasmic calcium concentration rise from inositol 1,4,5,-trisphosphate. J Biol Chem 1992; 267:5265–5271.PubMedGoogle Scholar
  77. 77.
    Choi OH, Kim JH, Kinet J-P. Calcium mobilization via sphingosine kinase in signaling by the FcεRI antigen receptor. Nature 1996; 380:634–636.PubMedGoogle Scholar
  78. 78.
    Melendez AJ, Floto RA, Cameron AJ et al. A molecular switch changes the signalling pathway used by FcγRI antibody receptor to mobilise calcium. Curr Biol 1998; 8:210–221.PubMedGoogle Scholar
  79. 79.
    Melendez A, Floto RA, Gillooly DJ et al. FcγRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking. J Biol Chem 1998; 273:9393–9402.PubMedGoogle Scholar
  80. 80.
    Melendez AJ, Bruetschy L, Floto RA et al. Functional coupling of FcγRI to nicotinamide dinucleotide phosphate (reduced form) oxidative burst and immune complex trafficking requires the activation of phospholipase D1. Blood 2001; 98:3421–3428.PubMedGoogle Scholar
  81. 81.
    Melendez AJ, Khaw AK. Dichotomy of Ca2+ signals triggered by different phospholipid pathways in antigen stimulation of human mast cells. J Biol Chem 2002; 277:17255–17262.PubMedGoogle Scholar
  82. 82.
    Rosales C, Jones SL, McCourt D et al. Bromophenacyl bromide binding to the actin-bundling protein 1-plastin inhibits inositol trisphosphate-independent increase in Ca2+ in human neutrophils. Proc Natl Acad Sci USA 1994; 91:3534–3538.PubMedGoogle Scholar
  83. 83.
    Olivera A, Rosenthal J, Spiegel S. Effect of acidic phospholipids on sphingosine kinase. J Cell Biochem 1996; 60:529–537.PubMedGoogle Scholar
  84. 84.
    Young JD, Ko SS, Cohn ZA. The increase in intracellular free calcium associated with IgG gamma 2b/gamma 1 Fc receptor-ligand interactions: Role in phagocytosis. Proc Nat Acad Sci USA 1984; 81:5430–5434.PubMedGoogle Scholar
  85. 85.
    Kobayashi K, Takahashi K, Nagasawa S. The role of tyrosine phosphorylation and Ca2+ accumulation in Fc gamma-receptormediated phagocytosis of human neutrophils. J Biochem (Tokyo) 1995; 117:1156–1161.PubMedGoogle Scholar
  86. 86.
    Della Bianca V, Grzeskowiak M, Rossi F. Studies on molecular regulation of phagocytosis and activation of the NADPH oxidase in neutrophils. IgG-and C3bmediated ingestion and associated respiratory burst independent of phospholipid turnover and Ca2+ transients. J Immunol 1990; 144:1411–1417.PubMedGoogle Scholar
  87. 87.
    Lew DP, Andersson T, Hed J et al. Ca2+-dependent and Ca2+-independent phagocytosis in human neutrophils. Nature 1985; 315:509–511.PubMedGoogle Scholar
  88. 88.
    Bengtsson T, Jaconi ME, Gustafson M et al. Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium. Eur J Cell Biol 1993; 62:49–58.PubMedGoogle Scholar
  89. 89.
    Jaconi ME, Lew DP, Carpentier JL et al. Cytosolic free calcium elevation mediates the phagosome lysosome fusion during phagocytosis in human neutrophils. J Cell Biol 1990; 110:1555–1564.PubMedGoogle Scholar
  90. 90.
    Greenberg S, el Khoury J, di Virgilio F et al. Ca2+-independent F-actin assembly and disassembly during Fc receptor-mediated phagocytosis in mouse macrophages. J Cell Biol 1991; 113:757–767.PubMedGoogle Scholar
  91. 91.
    Zimmerli S, Majeed M, Gustavsson M et al. Phagosome-lysosome fusion is a calcium-independent event in macrophages. J Cell Biol 1996; 132:49–61.PubMedGoogle Scholar
  92. 92.
    Edberg JC, Lin CT, Lau D et al. The Ca2+ dependence of human Fc gamma receptor-initiated phagocytosis. J Biol Chem 1995; 270:22301–22307.PubMedGoogle Scholar
  93. 93.
    Stendahl O, Krause KH, Krischer J et al. Redistribution of intracellular Ca2+ stores during phagocytosis in human neutrophils. Science 1994; 265:1439–1441.PubMedGoogle Scholar
  94. 94.
    Sawer DW, Sullivan JA, Mandell GL. Intracellular free calcium localization in neutrophils during phagocytosis. Science 1985; 230:663–666.Google Scholar
  95. 95.
    Bengtsson T, Jaconi ME, Gustafson M et al. Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium. Eur J Cell Biol 1993; 62:49–58.PubMedGoogle Scholar
  96. 96.
    Harris HE, Weeds AG. Plasma gelsolin caps and severs actin filaments. FEBS Lett 1984; 177:184–188.PubMedGoogle Scholar
  97. 97.
    Yin HL, Albrecht JH, Fattoum A. Identification of gelsolin, a Ca2+-dependent regulatory protein of actin gel-sol transformation, and its intracellular distribution in a variety of cells and tissues. J Cell Biol 1981; 91:901–906.PubMedGoogle Scholar
  98. 98.
    Serrander L, Skarman P, Rasmussen B et al. Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine neutrophils. J Immunol 2000; 165:2451–2457.PubMedGoogle Scholar
  99. 99.
    Allen LA, Aderem A. Molecular definition of distinct cytoskeletal structures involved in complement-and Fc receptor-mediated phagocytosis in macrophages. J Exp Med 1996; 184:627–637.PubMedGoogle Scholar
  100. 100.
    Allen LH, 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.PubMedGoogle Scholar
  101. 101.
    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
  102. 102.
    Greenberg S, Chang P, Silverstein SC. Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages. J Exp Med 1993; 177:529–534.PubMedGoogle Scholar
  103. 103.
    Zheleznyak A, Brown EJ. Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C activation. Evidence for protein kinase C translocation to phagosomes. J Biol Chem 1992; 267:12042–12048.PubMedGoogle Scholar
  104. 104.
    Dekker LV, Leitges M, Altschuler G et al. Protein kinase C-beta contributes to NADPH oxidase activation in neutrophils. Biochem J 2000; 347:285–289.PubMedGoogle Scholar
  105. 105.
    Melendez AJ, Harnett MM, Allen JM. Differentiation dependent switch in protein kinase C isoenzyme activation by FcgammaRI, the human high-affinity receptor for immunoglobulin G. Immunology 1999; 96:457–464.PubMedGoogle Scholar
  106. 106.
    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
  107. 107.
    Li J, Aderem A. MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates. Cell 1992; 70:791–801.PubMedGoogle Scholar
  108. 108.
    Hartwig JH, Thelen M, Rosen A et al. MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calciumcalmodulin. Nature 1992; 356:618–622.PubMedGoogle Scholar
  109. 109.
    Carballo E, Pitterle DM, Stumpo DJ et al. Phagocytic and macropinocytic activity in MARCKS-deficient macrophages and fibroblasts. Am J Physiol 1999; 277:C163–173.PubMedGoogle Scholar
  110. 110.
    Underhill DM, Chen J, Allen LA et al. MacMARCKS is not essential for phagocytosis in macrophages. J Biol Chem 1998; 273:33619–33623.PubMedGoogle Scholar
  111. 111.
    Zhu Z, Bao Z, Li J. MacMARCKS mutation blocks macrophage phagocytosis of zymosan. J Biol Chem 1995; 270:17652–17655.PubMedGoogle Scholar
  112. 112.
    Colombo MI, Beron W, Stahl PD. Calmodulin regulates endosome fusion. J Biol Chem 1997; 272:7707–7712.PubMedGoogle Scholar
  113. 113.
    Wickner W, Haas A. Yeast homotypic vacuole fusion: A window on organelle trafficking mechanisms. Annu Rev Biochem 2000; 69:247–275.PubMedGoogle Scholar
  114. 114.
    Zimmerli S, Majeed M, Gustavsson M et al. Phagosome-lysosome fusion is a calcium-independent event in macrophages. J Cell Biol 1996; 132:49–61.PubMedGoogle Scholar
  115. 115.
    Jaconi ME, Lew DP, Carpentier JL et al. Cytosolic free calcium elevation mediates the phagosome-lysosome fusion during phagocytosis in human neutrophils. J Cell Biol 1990; 110:1555–1564.PubMedGoogle Scholar
  116. 116.
    Downey GP, Botelho RJ, Butler JR et al. Phagosomal maturation, acidification, and inhibition of bacterial growth in nonphagocytic cells transfected with FcγRIIA receptors. J Biol Chem 1999; 274:28436–28444.PubMedGoogle Scholar
  117. 117.
    Wilsson A, Lundqvist H, Gustafsson M et al. Killing of phagocytosed Staphylococcus aureus by human neutrophils requires intracellular free calcium. J Leuk Biol 1996; 59:902–907.Google Scholar
  118. 118.
    Jahraus A, Egeberg M, Hinner B et al. ATP-dependent membrane assembly of F-actin facilitates membrane fusion. Mol Biol Cell 2001; 12:155–170.PubMedGoogle Scholar
  119. 119.
    Ferrari G, Langen H, Naito M et al. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 1999; 97:435–447.PubMedGoogle Scholar
  120. 120.
    Greenberg S, el Khoury J, di Virgilio F et al. Ca2+-independent F-actin assembly and disassembly during Fc receptor-mediated phagocytosis in mouse macrophages. J Cell Biol 1991; 113:757–767.PubMedGoogle Scholar
  121. 121.
    Ernst JD. Annexin III translocates to the periphagosomal region when neutrophils ingest opsonized yeast. J Immunol 1991; 146:3110–3114.PubMedGoogle Scholar
  122. 122.
    Majeed M, Perskvist N, Ernst JD et al. Roles of calcium and annexins in phagocytosis and elimination of an attenuated strain of Mycobacterium tuberculosis in human neutrophils. Microb Pathog 1998; 24:309–320.PubMedGoogle Scholar
  123. 123.
    Malik ZA, Iyer SS, Kusner DJ. Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: Contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. J Immunol 2001; 166:3392–3401.PubMedGoogle Scholar

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© and Springer Science+Business Media 2005

Authors and Affiliations

  • Alirio J. Melendez
    • 1
  1. 1.Department of Physiology Faculty of MedicineNational University of SingaporeSingapore

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