Immunologic Research

, Volume 34, Issue 2, pp 97–115 | Cite as

Development, migration, and survival of mast cells



Mast cells play a pivotal role in immediate hypersensitivity and chronic allergic reactions that can contribute to asthma, atopic dermatitis, and other allergic diseases. Because mast cell numbers are increased at sites of inflammation in allergic diseases, pharmacologic intervention into the proliferation, migration, and survival (or apoptosis) of mast cells could be a promising strategy for the management of allergic diseases. Mast cells differentiate from multipotent hematopoietic progenitors in the bone marrow. Stem cell factor (SCF) is a major chemotactic factor for mast cells and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of mast cells. Therefore, many aspects of mast cell biology can be understood as interactions of mast cells and their precursors with SCF and factors that modulate their responses to SCF and its signaling pathways. Numerous factors known to have such a capacity include cytokines that are secreted from activated T cells and other immune cells including mast cells themselves. Recent studies also demonstrated that monomeric IgE binding to FcωRI can enhance mast-cell survival. In this review we discuss the factors that regulate mast cell development, migration, and survival.

Key Words

Mast cell Development Proliferation Migration Survival Apoptosis SCF Kit IL-3 IgE 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Metcalfe DD, Baram D, Mekor YA: Mast cells. Physiol Rev 1997; 77(4):1033–1079.PubMedGoogle Scholar
  2. 2.
    Galli SJ, Maurer M, Lantz CS: Mast cells as sentinels of innate immunity. Curr Opin Immunol 1999; 11(1):53–59.PubMedGoogle Scholar
  3. 3.
    Secor VH, Secor WE, Gutekunst CA, Brown MA: Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J Exp Med 2000; 191(5):813–822.PubMedGoogle Scholar
  4. 4.
    Lee DM, Friend DS, Gurish MF, Benoist C, Mathis D, Brenne MB: Mast cells: a cellularlink between autoan-tibodies, and inflammatory arthritis. Science 2002; 297(5587):1689–1692.PubMedGoogle Scholar
  5. 5.
    Hara M, Ono K, Hwang MW, et al: Evidence for a role of mast cells in the evolution to congestive heart failure. J Exp Med 2002; 195(3):375–381.PubMedGoogle Scholar
  6. 6.
    Viegas M, Gomez E, Brooks J, Davies RJ: Changes in nasal mast cell numbers in and out of the pollen season. Int Arch Allergy Appl Immunol 1987;82(3–4):275–276.PubMedGoogle Scholar
  7. 7.
    Gibson PG, Allen CJ, Yang JP, et al: Intraepithelial mast cells in allergic and nonallergic asthma. Assessment using bronchial brushings. Am Rev Respir Dis 1993 148(1):80–86.PubMedGoogle Scholar
  8. 8.
    Kitamura Y, Ito A: Mast cell-committed progenitors. Proc Natl Acad Sci USA 2005; 102(32):11129–11130.PubMedGoogle Scholar
  9. 9.
    Kitamura Y, Yokoyama M, Matsuda H, Ohno T, Mori KJ. Spleen colony-forming cell as common precursor for tissue mast cells and granulocytes. Nature 1981; 291(5811):159–160.PubMedGoogle Scholar
  10. 10.
    Kitamura Y, Go S, Hatanaka K Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 1978; 52(2):447–452.PubMedGoogle Scholar
  11. 11.
    Rodewald HR, Dessing M, Dvorak AM, Galli SJ: Identification of a committed precursor for the mast cell lineage. Science 1996; 271(5250):818–822.PubMedGoogle Scholar
  12. 12.
    Chen CC, Grimbaldeston MA, Tsai M, Weissman IL, Galli SJ: Identification of mast cell progenitors in adult mice. Proc Natl Acad Sci USA 2005; 102(32):11408–11413.PubMedGoogle Scholar
  13. 13.
    Arinobu Y, Iwasaki H, Gurish MF, et al: Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. Proc Natl Acad Sci USA 2005; 102(50):18105–18110.PubMedGoogle Scholar
  14. 14.
    Jamur MC, Grodzki AC, Berenstein EH, Hamawy MM, Siraganian RP, Oliver C: Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 2005; 105(11):4282–4289.PubMedGoogle Scholar
  15. 15.
    Kirshenbaum AS, Kessler SW, Goff JP, Metcalfe DD. Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. J Immunol 1991; 146(5):1410–1415.PubMedGoogle Scholar
  16. 16.
    Castells MC, Friend DS, Bunnell CA, et al: The presence of membrane-bound stem cell factor on highly immature nonmetachromatic mast cells in the peripheral blood of a patient with aggressive systemic mastocytosis. J Allergy Clin Immunol 1996; 98(4) 831–840.PubMedGoogle Scholar
  17. 17.
    Rottem M, Okada T, Goff JP, Metcalfe DD: Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/FcωRI cell population. Blood 1994; 84(8):2489–2496.PubMedGoogle Scholar
  18. 18.
    Kempuraj D, Saito H, Kaneko A, et al: Characterization of mast cell-committed progenitors present in human umbilical cord blood. Blood 1999; 93(10):3338–3346.PubMedGoogle Scholar
  19. 19.
    Kirshenbaum AS, Goff JP, Semere T, Foster B, Scott LM, Metcalfe DD: Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood 1999; 94(7):2333–2342.PubMedGoogle Scholar
  20. 20.
    Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 1988; 335(6185):88–89.PubMedGoogle Scholar
  21. 21.
    Copeland NG, Gilbert DJ, Cho BC, et al: Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 1990; 63(1):175–183.PubMedGoogle Scholar
  22. 22.
    Sawai N, Koike K, Mwamtemi HH, et al: Thrombopoietin augments stem cell factor-dependent growth of human mast cells from bone marrow multipotential hematopoietic progenitors. Blood 1999; 93(11):3703–3712.PubMedGoogle Scholar
  23. 23.
    Nakahata T, Kobayashi T, Ishiguro A, et al: Extensive proliferation of mature connective-tissue type mast cells in vitro. Nature 1986; 324(6092):65–67.PubMedGoogle Scholar
  24. 24.
    Tsuji K, Nakahata T, Takagi M, et al: Effects of interleukin-3 and interleukin-4 on the development of “connective tissue-type” mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3. Blood 1990; 75(2):421–427.PubMedGoogle Scholar
  25. 25.
    Bressler RB, Thompson HL, Keffer JM, Metcalfe DD: Inhibition of the growth of IL-3-dependent mast cells from murine bone marrow by recombinant granulocyte macrophage-colony-stimulating factor. J Immunol 1989; 143(1):135–139.PubMedGoogle Scholar
  26. 26.
    Saito H, Ebisawa M, Tachimoto H, et al: Selective growth of human mast cells induced by Steel factor, IL-6, and prostaglandin E2 from cord blood mononuclear cells. J Immunol 1996; 157(1):343–350.PubMedGoogle Scholar
  27. 27.
    Kinoshita T, Sawai N, Hidaka E, Yamashita T, Koike K: Interleukin-6 directly modulates stem cell factor-dependent development of human mast cells derived from CD34(+) cord blood cells. Blood 1999; 94(2):496–508.PubMedGoogle Scholar
  28. 28.
    Saito H: Culture of human mast cells from hemopoietic progenitors. Methods Mol Biol 2005; 315:113–122.Google Scholar
  29. 29.
    Hamaguchi Y, Kanakura K, Fujita J, et al: Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells. J Exp Med 1987; 165(1):268–273.PubMedGoogle Scholar
  30. 30.
    Nilsson G, Miettinen U, Ishizaka T, Ashman LK, Irani AM, Schwartz LB: Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells. Blood 1994; 84(5):1519–1527.PubMedGoogle Scholar
  31. 31.
    Sillaber C, Sperr WR, Agis H, Spanblochl E, Lechner K, Valent P: Inhibition of stem cell factor dependent formation of human mast cells by interleukin-3 and interleukin-4. Int Arch Allergy Immunol 1994; 105(3):264–268.PubMedGoogle Scholar
  32. 32.
    Xia HZ, Du Z, Craig S, et al: Effect of recombinant human IL-4 on tryptase, chymase, and Feω receptor type I expression in recombinant human stem cell factor-dependent fetal liver-derived human mast cells. J Immunol 1997; 159(6):2911–2921.PubMedGoogle Scholar
  33. 33.
    Oskeritzian CA, Wang Z, Kochan JP, et al: Recombinant human (rh)IL-4-mediated apoptosis and recombinant human IL-6-mediated protection of recombinant human stem cell factor-dependent human mast cells derived from cord blood mononuclear cell progenitors. J Immunol 1999; 163(9):5105–5115.PubMedGoogle Scholar
  34. 34.
    Bischoff SC, Sellge G, Lorentz A, Sebald W, Raab R, Manns MP: IL-4 enhances proliferation and mediator release in mature human mast cells. Proc Natl Acad Sci USA 1999; 96(14):8080–8085.PubMedGoogle Scholar
  35. 35.
    Eklund KK, Ghildyal N, Austen KF, Stevens RL: Induction by IL-9 and suppression by IL-3 and IL-4 of the levels of chromosome 14-derived transcripts that encode late-expressed mouse mast cell proteases. J Immunol 1993; 151(8):4266–4273.PubMedGoogle Scholar
  36. 36.
    Thompson-Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, Rennick DM: Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med 1991; 173(2):507–510.PubMedGoogle Scholar
  37. 37.
    Ochi H, Hirani WM, Yuan Q, Friend DS, Austen KF, Boyce JA: T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J Exp Med 1999; 190(2):267–280.PubMedGoogle Scholar
  38. 38.
    Matsuzawa S, Sakashita K, Kinoshita T, Ito S, Yamashita T, Koike K: IL-9 enhances the growth of human mast cell progenitors under stimulation with stem cell factor. J Immunol 2003; 170(7):3461–3467.PubMedGoogle Scholar
  39. 39.
    Takagi M, Koike K, Nakahata T: Antiproliferative effect of IFN-ψ on proliferation of mouse connective tissue-type mast cells. J Immunol 1990; 145(6):1880–1884.PubMedGoogle Scholar
  40. 40.
    Kirshenbaum AS, Worobec AS, Davis TA, Goff JP, Semere T, Metcalfe DD: Inhibition of human mast cell growth and differentiation by interferon ψ-1b. Exp Hematol 1998; 26(3):245–251.PubMedGoogle Scholar
  41. 41.
    Mann-Chandler MN, Kashyap M, Wright HV, et al: IFN-ψ induces apoptosis in developing mast cells. J Immunol 2005; 175(5):3000–3005.PubMedGoogle Scholar
  42. 42.
    Fiehn C, Prummer O, Gallati H, Heilig B, Hunstein W: Treatment of systemic mastocytosis with interferon-ψ: failure after appearance of anti-IFN-ψ antibodies. Eur J Clin Invest 1995; 25(8):615–618.PubMedGoogle Scholar
  43. 43.
    Hu ZQ, Kobayashi K, Zenda N, Shimamura T: Tumor necrosis factor-α- and interleukin-6-triggered mast cell development from mouse spleen cells. Blood 1997; 89(2):526–533PubMedGoogle Scholar
  44. 44.
    Yuan Q, Gurish MF, Friend DS, Austen KF, Boyce JA. Generation of a novel stem cell factor-dependent mast cell progenitor. J Immunol 1998; 161(10):5143–5146.PubMedGoogle Scholar
  45. 45.
    Yanagida M, Fukamachi H, Ohgami K, et al: Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells. Blood 1995; 86(10):3705–3714.PubMedGoogle Scholar
  46. 46.
    Matsida H, Kannan Y, Ushio H, et al: Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells. J Exp Med 1991; 174(1):7–14.Google Scholar
  47. 47.
    Kanbe N, Kurosawa M, Miyachi Y, Kanbe M, Saitoh H, Matsuda H: Nerve growth factor prevents apoptosis of cord blood-derived human cultured mast cells synegistically with stem cell factor. Clin Exp Allergy 2000; 30(8):1113–1120.PubMedGoogle Scholar
  48. 48.
    Broide DH, Wasserman SI, Alvaro-Gracia J, Zvaifler NJ, Firestein GS: Transforming growth factor-β1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation. J Immunol 1989; 143(5):1591–1597.PubMedGoogle Scholar
  49. 49.
    Gebhardt T, Lorentz A, Detmer F, et al: Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor β1. Gut 2005; 54(7):928–934.PubMedGoogle Scholar
  50. 50.
    Kobayashi M, Laver JH, Kato T, Miyazaki H, Ogawa M: Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3. Blood 1996; 88(2):429–436.PubMedGoogle Scholar
  51. 51.
    Kobayashi M, Laver JH, Lyman SD, Kato T, Miyazaki H, Ogawa M: Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture. Int J Hematol 1997; 66(4):423–434.PubMedGoogle Scholar
  52. 52.
    Roskoski Jr, R: Signaling by Kit protein-tyrosine kinase—the stem cell factor receptor. Biochem Biophys Res Commun 2005; 337(1):1–13.PubMedGoogle Scholar
  53. 53.
    Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R: Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells 2005; 23(1):16–43PubMedGoogle Scholar
  54. 54.
    Koyasu S, Minowa A, Terauchi Y, Kadowaki T, Matsuda S: The role of phosphoinositide-3-kinase in mast cell homing to the gastrointestinal tract. Mast cells and basophils: development, activation and roles in allergic/ autoimmune disease. Chichester, England, John Wiley & Sons Ltd, 2005, pp 152–165.Google Scholar
  55. 55.
    Koyasu S: The role of PI3K in immune cells. Nat Immunol 2003; 4(4):313–319.PubMedGoogle Scholar
  56. 56.
    Okkenhaug K, Vanhaesebroeck B: PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 2003; 3(4):317–330.PubMedGoogle Scholar
  57. 57.
    Fukao T, Yamada T, Tanabe M, et al: Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol 2002; 3(3):295–304.PubMedGoogle Scholar
  58. 58.
    Ali K, Bilancio A, Thomas M, et al: Essential role for the p110σ phosphoinositide 3-kinase in the allergic response. Nature 2004; 431(7011):1007–1011.PubMedGoogle Scholar
  59. 59.
    Agosti V, Corbacioglu S, Ehlers I, et al: Critical role for Kit-mediated Src kinase but not PI 3-kinase signaling in pro T and pro B cell development. J Exp Med 2004; 199(6):867–878.PubMedGoogle Scholar
  60. 60.
    Kissel H, Timokhina I, Hardy MP, et al: Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses. EMBO J 2000; 19(6):1312–1326.PubMedGoogle Scholar
  61. 61.
    Gu H, Saito K, Klama LD, et al: Essential role for Gab2 in the allergic response. Nature 2001; 412(6843):186–190.PubMedGoogle Scholar
  62. 62.
    Hirsch E, Katanaev VL, Garlanda C, et al: Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 2000; 287(5455):1049–1053.PubMedGoogle Scholar
  63. 63.
    Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D: Roles of PLC-β2 and-β3 and PI3Kψ in chemoattractant-mediated signal transduction. Science 2000; 287(5455):1046–1049.PubMedGoogle Scholar
  64. 64.
    Sasaki T, Irie-Sasaki J, Jones RG, et al: Function of PI3Kψ in thymocyte development, T cell activation, and neutrophil migration. Science 2000; 287(5455):1040–1046.PubMedGoogle Scholar
  65. 65.
    Shelburne CP, McCoy ME, Piekorz R, et al: Stat5 expression is critical for mast cell development and survival. Blood 2003; 102(4):1290–1297.PubMedGoogle Scholar
  66. 66.
    Brizzi MF, Zini MG, Aronica MG, Blechman JM, Yarden Y, Pegoraro L: Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase. J Biol Chem 1994; 269(50):31680–31684.PubMedGoogle Scholar
  67. 67.
    Weiler SR, Mou S, DeBerry CS, et al: JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. Blood 1996; 87(9):3688–3693.PubMedGoogle Scholar
  68. 68.
    Linnekin D, Weiler SR, Mou S, et al: JAK2 is constitutively associated with c-Kit and is phosphorylated in response to stem cell factor. Acta Haematol 1996; 95(3–4):224–228.PubMedGoogle Scholar
  69. 69.
    Brizzi MF, Dentelli P, Rosso A, Yarden Y, Pegoraro L: STAT protein recruitment and activation in c-Kit deletion mutants. J Biol Chem 1999; 274(24):16965–16972PubMedGoogle Scholar
  70. 70.
    Hundley TR, Gilfillan AM, Tkaczyk C, Andrade MV, Metcalfe DD, Beaven MA: Kit and FcωRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells. Blood 2004; 104(8):2410–2417.PubMedGoogle Scholar
  71. 71.
    Suzuki K, Nakajima H, Watanabe N, et al: Role of common cytokine receptor gamma chain (ψc)- and Jak3-dependent signaling in the proliferation and survival of murine mast cells. Blood 2000; 96(6):2172–2180.PubMedGoogle Scholar
  72. 72.
    Stevens RL, Morokawa N, Wang J, Krilis SA: RasGRP4 in mast cell signalling and disease susceptibility. Chichester, England: John Wiley & Sons Ltd, 2005, pp 54–77.Google Scholar
  73. 73.
    Li L, Yang Y, Wong GW, Stevens RL: Mast cells in airway hyporesponsive C3H/HeJ mice express a unique isoform of the signaling protein Ras guanine nucleotide releasing protein 4 that is unresponsive to diacylglycerol and phorbol esters. J Immunol 2003; 171(1):390–397PubMedGoogle Scholar
  74. 74.
    Li L, Yang Y, Stevens RL: RasGRP4 regulates the expression of prostaglandin D2 in human and rat mast cell lines. J Biol Chem 2003; 278(7):4725–4729.PubMedGoogle Scholar
  75. 75.
    Kirtamura Y.: MITF and SgIGSF: an esential transcrption factor and its target adhesion molecule for development and survival of mast cells. Mast cells and basophils: development, activation and roles in allergic/autoimmune disease. Chichester, England: John Wiley & Sons Ltd 2005, pp 4–14.Google Scholar
  76. 76.
    Morii E, Oboki K, Ishihara K, Jippo T, Hirano T, Kitamura Y: Roles of MITF for development of mast cells in mice: effects on both precursors and tissue environments. Blood 2004; 104(6):1656–1661.PubMedGoogle Scholar
  77. 77.
    Morii E, Oboki K: MITF is necessary for generation of prostaglandin D2 in mouse mast cells. J Biol Chem 2004; 279(47):48923–48929.PubMedGoogle Scholar
  78. 78.
    Ito A, Jippo T, Wakayama T, et al: SgIGSF: a new mast-cell adhesion molecule used for attachment to fibroblasts and transcriptionally regulated my MITF. Blood 2003; 101(7):2601–2608.PubMedGoogle Scholar
  79. 79.
    Razin E, Zhang ZC, et al: Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells. J Biol Chem 1999; 274(48):34272–34276.PubMedGoogle Scholar
  80. 80.
    Levy C, Nechushtan H, Razin E: A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor. J Biol Chem 2002; 277(3):1962–1966.PubMedGoogle Scholar
  81. 81.
    Sonnenblick A, Levy C, Razin E: Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes. Mol Cell Biol 2004; 24(24):10584–10592.PubMedGoogle Scholar
  82. 82.
    Yamamoto M, Takahashi S, Onodera K, Muraosa Y, Engel JD: Upstream and downstream of erythroid transcription factor GATA-1. Genes Cells 1997; 2(2):107–115.PubMedGoogle Scholar
  83. 83.
    Harigae H, Takahashi S, Suwabe N, et al.: Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells. Genes Cells 1998; 3(1):39–50.PubMedGoogle Scholar
  84. 84.
    Pevny L, Lin CS, D'Agati V, Simon MC, Orkin SH, Costantini F: Development of hematopoietic cells lacking transcription factor GATA-1. Development 1995; 121(1):163–172.PubMedGoogle Scholar
  85. 85.
    Migliaccio AR, Rana RA, Sanchez M, et al.: GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-How mouse mutant. J Exp Med 2003; 197(3):281–296.PubMedGoogle Scholar
  86. 86.
    Zon LI, Gurish MF, Stevens RL, et al: GATA-binding transcription factors in mast cells regulated the promoter of the mast cell carboxypeptidase A gene. J Biol Chem 1991; 266(34):22948–22953.PubMedGoogle Scholar
  87. 87.
    Nishiyama C, Yokota T, Okumura K, Ra C: The transcription factors Elf-1 and GATA-1 bind to cell-specific enhancer elements of human high-affinity IgE recpetor α-chain gene. J Immunol 1991; 163(2):620–630.Google Scholar
  88. 88.
    Nishiyama C, Hasegawa M, Nishiyama M, et al.: Regulation of human FcεRI α-chain gene expression by multiple transcription factors. J Immunol 2002; 168(9):4546–4552.PubMedGoogle Scholar
  89. 89.
    Maeda K, Nishiyama C, Tokura T, et al.: Regulation of cell type-specific mouse FcεRI β-chain gene expression by GATA-1 via four GATA motifs in the promoter. J Immunol 2003; 170(1):334–340.PubMedGoogle Scholar
  90. 90.
    Nishiyama C, Ito T, Nishiyama M, et al.: GATA-1 is required for expression of FcεRI on mast cells: analysis of mast cells derived from GATA-1 knock-down mouse bone marrow. Int Immunol 2005; 17(7):847–856.PubMedGoogle Scholar
  91. 91.
    Tsai FY, Orkin SH: Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 1997; 89(10):3636–3643.PubMedGoogle Scholar
  92. 92.
    Walsh JC, DeKoter RP, Lee HJ et al: Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates. Immunity 2002; 17(5):665–676.PubMedGoogle Scholar
  93. 93.
    Nishiyama C, Nishiyama M, Ito T, et al: Overproduction of PU.1 in mast cell progenitors: its effect on monocyte-and mast cell-specific gene expression. Biochem Biophys Res Commun 2004; 313(3):516–521.PubMedGoogle Scholar
  94. 94.
    Ito T, Nishiyama C, Nishiyama M, et al: Mast cells acquire monocyte-specific gene expression and monocyte-like morphology by overproduction of PU.1. J Immunol 2005; 174(1):376–383.PubMedGoogle Scholar
  95. 95.
    Dahl R, Walsh JC, Lancki D, et al: Regulation of macrophage and neutrophil cell fates by the PU.1: C/EBPα ratio and granulocyte colony-stimulating factor. Nat Immunol 2003; 4(10):1029–1036.PubMedGoogle Scholar
  96. 96.
    Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG: Absence of granulocyte colonystimulating factor signaling and neutrophil development in CCAAT enhancer binding protein α-deficient mice. Proc Natl Acad Sci USA 1997; 94(2):569–574.PubMedGoogle Scholar
  97. 97.
    Gurish MF, Tao H, Abonia JP, et al: Intestinal mast cell progenitors require CD49dβ7 (α4βq7 integrin) for tissue-specific homing. J Exp Med 2001; 194(9):1243–1252.PubMedGoogle Scholar
  98. 98.
    Boyce JA, Mellor EA, Perkins B, Lim YC, Luscinskas FW: Human mast cell progenitors use α4-integrin, VCAM-1, and PSGL-1 E-selection for adhesive interactions with human vascular endothelium under flow conditions. Blood 2002; 99(8):2890–2896.PubMedGoogle Scholar
  99. 99.
    Humbles AA, Lu B, Friend DS, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci USA 2002; 99(3):1479–1484.PubMedGoogle Scholar
  100. 100.
    Brightling CE, Ammit AJ, Kaur D, et al.: Bradding. The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 2005; 171(10):1103–1108.PubMedGoogle Scholar
  101. 101.
    Ishizuka T, Okajima F, Ishiwara M, et al.: Sensitized mast cells migrate toward the antigen: a response regulated by p38 mitogen-activated protein kinase and Rho-associated coiled-coil-forming protein kinase. J Immunol 2001; 167(4):2298–2304.PubMedGoogle Scholar
  102. 102.
    Olivera A, Rivera J: Sphingolipids and the balancing of immune cell fuction: lessons from the mast cell. J Immunol 2005; 174(3):1153–1158.PubMedGoogle Scholar
  103. 103.
    Jolly PS, Bektas M, Olivera A, et al.: Transactivation of sphingosine-1-phosphate receptors by FcεRI triggering is required for normal mast cell degranulation and chemotaxis. J Exp Med 2004; 199(7):959–970.PubMedGoogle Scholar
  104. 104.
    Urtz N, Olivera A, Bofill-Cardona E, et al: Early activation of sphingosine kinase in mast cells and recruitment to FcεRI are mediated by its interaction with Lyn kinase. Mol Cell Biol 2004; 24(19): 8765–8777.PubMedGoogle Scholar
  105. 105.
    Olivera A, Urtz N, Mizugishi K, et al: IgE-dependent activation of spingosine kinase 1 and 2 and secretion of sphingosine-1-phosphate requires FYN kinase and contributes to mast cell responses. J Biol Chem 2005; 281(5):2515–2525.PubMedGoogle Scholar
  106. 106.
    Kitaura J, Kinoshita T, Matsumoto M, et al: IgE- and IgE-Ag-mediated mast cell migration in an autocrine/paracrine fashion. Blood 2005; 105(8):3222–3229.PubMedGoogle Scholar
  107. 107.
    Droin NM, Green DR: Role of Bcl-2 family members in immunity and disease. Biochim Biophys Acta 2004; 1644(2–3):179–188.PubMedGoogle Scholar
  108. 108.
    Kuwana T, Newmeyer DD: Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 2003; 15(6):691–699.PubMedGoogle Scholar
  109. 109.
    Maurer M, Tsai M, Metz M, Fish S, Korsmeyer SJ, Galli SJ: A role for Bax in the regulation of apoptosis in mouse mast cells. J Invest Dermatol 2000; 114(6):1205–1206.PubMedGoogle Scholar
  110. 110.
    Cheng EH, Wei MC, Weiler S, et al.: BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 2001; 8(3):705–711.PubMedGoogle Scholar
  111. 111.
    Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB: BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev 2001; 15(12):1481–1486.PubMedGoogle Scholar
  112. 112.
    Mekori YA., Gilfillan AM, Akin C, Hartmann K, Metcalfe DD. Human mast cell apoptosis is regulated through Bcl-2 and Bcl-XL. J Clin Immunol 2001; 21(3):171–174.PubMedGoogle Scholar
  113. 113.
    Baghestanian M, Jordan JH, Kiener HP, et al: Activation of human mast cells through stem cell factor receptor (KIT) is associated with expression of bcl-2. Int Arch Allergy Immunol 2002; 129(3):228–236.PubMedGoogle Scholar
  114. 114.
    Xiang Z, Ahmed AA, Moller C, Nakayama K, Hatakeyama S, Nilsson G: Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. J Exp Med 2001; 194(11):1561–1569.PubMedGoogle Scholar
  115. 115.
    Datta SR, Dudek H, Tao X, et al.: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91(2):231–241.PubMedGoogle Scholar
  116. 116.
    del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G: Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 1997; 278(5338):687–689.PubMedGoogle Scholar
  117. 117.
    Blume-Jensen P, Janknecht R, Hunter T: The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol 1998; 8(13):779–782.PubMedGoogle Scholar
  118. 118.
    Ranger AM, Zha J, Harada H, et al: Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci USA 2003; 100(16):9324–9329.PubMedGoogle Scholar
  119. 119.
    Brunet A, Bonni A, Zigmond MJ, et al.: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96(6):857–868.PubMedGoogle Scholar
  120. 120.
    Rena G, Guo S, Cichy SC, Unterman TG, Cohen P: Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem 1999;274(24):17179–17183.PubMedGoogle Scholar
  121. 121.
    Dijkers PF, Birkenkamp KU, Lam EW, et al.: FKHR-L1 can act as a critical effector of cell death induced by cytokine withdrawal: protein kinase B-enhanced cell survival through maintenance of mitochondrial integrity. J Cell Biol 2002; 156(3):531–542.PubMedGoogle Scholar
  122. 122.
    Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ: Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol 2000; 10(19):1201–1204.PubMedGoogle Scholar
  123. 123.
    Alfredsson J, Puthalakath H, Martin H, Strasser A, Nilsson G: Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation. Cell Death Differ 2005; 12(2):136–144.PubMedGoogle Scholar
  124. 124.
    Ley R, Balmanno K, Hadfield K, Weston C, Cook SJ: Activation of the ERK 1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim. J Biol Chem 2003; 278(21):18811–18816.PubMedGoogle Scholar
  125. 125.
    Luciano F, Jacquel A, Colosetti P, et al: Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene 2003; 24(43):6785–6793.Google Scholar
  126. 126.
    Kitaura J, Xiao W, Maeda-Yamamoto M, Kawakami Y, Lowell CA, Kawakami T: Early divergence of Fcε receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survival. J Immunol 2004; 173(7):4317–4323.PubMedGoogle Scholar
  127. 127.
    Kawakami T, Kitaura J: Mast cell survival and activation by IgE in the absence of antigen: a consideration of the biologic mechanisms and relevance. J Immunol 2005; 175(7):4167–4173.PubMedGoogle Scholar
  128. 128.
    Yoshikawa H, Nakajima Y, Tasaka K: Glucocorticoid suppresses autocrine survival of mast cells by inhibiting IL-4 production and ICAM-1 expression. J Immunol 1999; 162(10):6163–6170.Google Scholar
  129. 129.
    Yoshikawa H, Nakajima Y, Tasaka K: Enhanced expression of Fas-associated death domain-like IL-1-converting enzyme (FLICE)-inhibitory protein induces resistance to Fas-mediated apoptosis in activated mast cells. J Immunol 2000; 165(11):6262–6269.PubMedGoogle Scholar
  130. 130.
    Kitaura J, Song J, Tsai M, et al.: Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI. Proc Natl Acad Sci USA 2003; 100(22):12911–12916.PubMedGoogle Scholar
  131. 131.
    Asai K, Kitaura J, Kawakami Y, et al.: Regulation of mast cell survival by IgE. Immunity 2001; 14(6):791–800.PubMedGoogle Scholar
  132. 132.
    Kalesnikoff J, Huber M, Lam V, et al: Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 2001; 14(6):801–811.PubMedGoogle Scholar
  133. 133.
    Kohno M, Yamasaki S, Tybulewicz VL, Saito T: Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen. Blood 2005; 105(5):2059–2065.PubMedGoogle Scholar
  134. 134.
    Yamasaki S, Ishikawa E, Kohno M, Saito T: The quantity and duration of FcRγ signals determine mast cell degranulation and survival. Blood 2004; 103(8):3093–3101.PubMedGoogle Scholar
  135. 135.
    Bischoff SC, Sellge G, Manns MP, Lorentz, A: Interleukin-4 induces a switch of human intestinal mast cells from proinflammatory cells to Th2-type cells. Int Arch Allergy Immunol 2001; 124(1–3):151–154.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  1. 1.Research Unit for Allergy Transcriptome. Research Center for Allergy and ImmunologyRIKEN Yokohama InstituteYokohamaJapan
  2. 2.Division of Cell BiologyLa Jolla Institute for Allergy and ImmunologySan Diego

Personalised recommendations