International Journal of Hematology

, Volume 75, Issue 4, pp 350–356 | Cite as

Cytokines Regulate Development of Human Mast Cells from Hematopoietic Progenitors

  • Tatsutoshi Nakahata
  • Hano Toru
Progress in Hematology


Combination of stem cell factor (SCF) and interleukin-6 (IL-6) significantly promoted proliferation of human mast cells from cord blood CD34+ cells. Most of the cells, cultured in the presence of SCF and IL-6 for 10 weeks, expressedc-kit and contained a significant amount of histamine and tryptase and a low amount of chymase. Both tryptase-positive chymase-negative mast cells (MCT) and tryptase-positive chymase-positive mast cells (MCTC) were found in the same colony derived from a single cord blood CD34+ cell, suggesting that MCT and MCTC develop from common precursor cells. Single-cell culture of CD34+ cells revealed that committed mast cell progenitors are included in CD34+CD38+HLA-DR cells. IL-4 significantly enhanced high-affinity immunoglobulin E (IgE) receptor (FcεRI) α-chain messenger RNA expression and induced FcεRI on SCF-dependent cord blood-derived human mast cells, resulting in high histamine-releasing activity upon cross-linking of FcεRI. Another factor that up-regulated FcεRI was IgE, and a combination of IL-4 and IgE markedly augmented FcεRI expression on the mast cells. IL-4 and IgE may enhance FcεRI expression by distinct mechanisms; IL-4 promotes FcεRI α-chain gene transcription and thus increases α-chain protein synthesis in the cells, whereas the binding of IgE may anchor the FcεRI on the cell surface, resulting in suppression of internalization of FcεRI. Mast cells are progeny of hematopoietic stem cells. Recent discovery of a xenotransplantation model revealed that human hematopoietic stem cells can proliferate and differentiate into mature mast cells in the mouse skin 3 months after transplantation of human cord blood CD34+ cells, suggesting that this model may pave the way to clarification of the functions of human mast cells in vivo.

Key words

Human Mast cells Stem cell factor FcεRI Mast cell progenitor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ishizaka T, Ishizaka K.Activation of mast cells for mediator release through IgE receptors.Prog Allergy. 1984;34:188–235.PubMedGoogle Scholar
  2. 2.
    Ishizaka T, Conrad DH, Schulman ES, Sterk AR, Ko CG, Ishizaka K. IgE-mediated triggering signals for mediator release from human mast cells and basophils.Fed Proc. 1984;43:2840–2845.PubMedGoogle Scholar
  3. 3.
    Moller A, Henz BM, Grutzkau A, et al. Comparative cytokine gene expression: regulation and release by human mast cells.Immunology. 1998;93:289–295.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    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;291:159.CrossRefPubMedGoogle Scholar
  5. 5.
    Nakahata T, Spicer SS, Cantey JR, Ogawa M. Clonal assay of mouse mast cell colonies in methylcellulose culture.Blood. 1982; 60:352–361.PubMedGoogle Scholar
  6. 6.
    Furitsu T, Saito H, Dvorak AM, et al. Development of human mast cellsin vitro.Pro Natl Acad Sci U S A. 1989;86:10039–10043.CrossRefGoogle Scholar
  7. 7.
    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;146:1410–1415.PubMedGoogle Scholar
  8. 8.
    Irani AA, Craig SS, Nilsson G, Ishizaka T, Schwartz LB. Characterization of human mast cells developmentin vitro from fetal liver cells co-cultured with murine 3T3 fibroblasts.Immunology. 1992; 77:136–143.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Valent P, Spanblöchl E, Sperr WR, et al. Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit- ligand in long-term culture.Blood. 1992;80:2237–2245.PubMedGoogle Scholar
  10. 10.
    Kirshenbaum AR, Goff JP, Kessler SW, Mican JM, Zsebo KM, Metcalfe DD. Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells.J Immunol. 1992;148:772–777.PubMedGoogle Scholar
  11. 11.
    Irani AM, Nilsson G, Miettinen U, et al. Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells.Blood. 1992;80:3009–3021.PubMedGoogle Scholar
  12. 12.
    Mitsui H, Furitsu T, Dvorak AM, et al. Development of human mast cells from umbilical cord blood cells by recombinant human and murinec-kit ligand.Proc Natl Acad Sci U S A. 1993;90:735–739.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Durand B, Migliacco G, Yee NS, et al. Long-term generation of human mast cells in serum free-cultures of CD34+ cord blood cells stimulated with stem cell factor and interleukin-3.Blood. 1994;84: 3667–3674.PubMedGoogle Scholar
  14. 14.
    Nakahata T, Tsuji K, Tanaka R, et al. Synergy of stem cell factor and other cytokines in mast cell development. In: Kitamura Y, Yamamoto S, Galli SJ, Greaves MW, eds.Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function. New York: Raven Press; 1995:13–24.Google Scholar
  15. 15.
    Yin T, Taga T, Tsang ML, Yasukawa K, Kishimoto T, Yang YC. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction.J Immunol. 1993;151:2555–2561.PubMedGoogle Scholar
  16. 16.
    Toru H, Ra C, Nonoyama S, Suzuki K, Yata J, Nakahata T. Induction of the high-affinity IgE receptor (FcεRI) on human mast cells by IL-4.Int Immunol. 1996;8:1367–1373.CrossRefPubMedGoogle Scholar
  17. 17.
    Toru H, Kinashi T, Ra C, Nonoyama S, Yata J, Nakahata T. IL-4 induces homotypic aggregation of human cultured mast cells by promoting LFA-1/ICAM-1 adhesion molecules.Blood. 1997;89: 3296–3302.PubMedGoogle Scholar
  18. 18.
    Toru H, Eguchi M, Matsumoto R, Yanagida M, Yata J, Nakahata T. IL-4 promotes the development of tryptase and chymase double- positive human mast cells accompanied by cell maturation.Blood. 1998;1:187–195.Google Scholar
  19. 19.
    Kampuraj D, Saito H, Kaneko A, et al. Characterization of masT-cell-committed progenitors present in human cord blood.Blood. 1999;93:3338–3346.Google Scholar
  20. 20.
    Valent P, Bettelheim P. Cell surface structures of human basophils and mast cells: biochemical and functional characterization.Adv Immunol. 1992;52:333–423.CrossRefPubMedGoogle Scholar
  21. 21.
    Deaglio S, Morra M, Mallone R, et al. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member.J Immunol. 1998;160:395–402.PubMedGoogle Scholar
  22. 22.
    Irani AM, Schwartz LB. Mast cell heterogeneity.Clin Exp Allergy. 1989;19:143–155.CrossRefPubMedGoogle Scholar
  23. 23.
    Irani AM, Schechter NM, Craig SS, DeBlois G, Schwartz LB. Two types of mast cells that have distinct neutral protease compositions.Proc Natl Acad Sci U S A. 1986;83:4464–4468.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Schwartz LB. Monoclonal antibodies against human mast cell tryptase demonstrate shared antigenic sites on subunits of tryptase and selective localization of enzyme to mast cells.J Immunol. 1985; 134:526–531.PubMedGoogle Scholar
  25. 25.
    Schwartz LB. Mast cells: function and contents.Curr Opin Immunol. 1994;6:91–97.CrossRefPubMedGoogle Scholar
  26. 26.
    Craig SS, Schechter NM, Schwartz LB. Ultrastructural analysis of human T and TC mast cells identified by immunoelectron microscopy.Lab Invest. 1988;58:682–691.PubMedGoogle Scholar
  27. 27.
    Craig SS, Schechter NM, Schwartz LB. Ultrastructural analysis of maturing human T and TC mast cellsin situ.Lab Invest. 1989;60: 147–157.PubMedGoogle Scholar
  28. 28.
    Ishizaka T, Mitsui H, Yanagida M, Miura T, Dvorak AM. Development of human mast cells from their progenitors.Curr Opin Immunol. 1993;5:937–943.CrossRefPubMedGoogle Scholar
  29. 29.
    Dvorak AM. Human mast cells, Ultrastructural observation ofin situ, ex vivo, andin vitro sites, sources, and systems. In: Kaliner MA, Metcalfe DD, eds.The Mast Cell in Health and Disease. New York: Marcel Dekker; 1992:1–90.Google Scholar
  30. 30.
    Dvorak AM, Massey W, Warner J, Kissell S, Kagey-Sobotka A, Lichtenstein LM. IgE-mediated anaphylactic degranulation of isolated human skin mast cells.Blood. 1991;77:569–578.PubMedGoogle Scholar
  31. 31.
    Dvorak AM, Furitu T, Ishizaka T. Ultrastructural morphology of human mast cell progenitors in sequential cocultures of cord blood cells and fibroblasts.Int Arch Allergy Immunol. 1993;100:219–229.CrossRefPubMedGoogle Scholar
  32. 32.
    Dvorak AM, Seder RA, Paul WE, Morgan ES, Galli SJ. Effects of interleukin-3 with or without thec-kit ligand, stem cell factor, on the survival and cytoplasmic granule formation of mouse basophils and mast cellsin vitro.Am J Pathol. 1994;144:160–170.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Nakano T, Sonoda T, Hayashi C, et al. Fate of bone marrow- derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice.J Exp Med. 1985;162:1025–1043.CrossRefPubMedGoogle Scholar
  34. 34.
    Kobayashi T, Nakano T, Nakahata T, et al. Formation of mast cell colonies in methylcellulose by mouse peritoneal cells and differentiation of these cloned cells in both the skin and the gastric mucosa of W/Wv mice: evidence that a common precursor can give rise to both “connective tissue-type” and “mucosal” mast cells.J Immunol. 1986;136:1378–1384.PubMedGoogle Scholar
  35. 35.
    Gurich MF, Pear WS, Stevens RL, et al. Tissue-regulated differentiation and maturation of av-abl-immortalized mast cell-committed progenitor.Immunity. 1995;3:175–186.CrossRefGoogle Scholar
  36. 36.
    Levi-Schaffer F, Austen KF, Gravallese PM, Stevens RL. Coculture of interleukin 3-dependent mouse mast cells with fibroblasts results in a phenotypic change of the mast cells.Proc Natl Acad Sci U S A. 1986;83:6485–6488.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Tsai M,Takeishi T, Thompson H, et al. Induction of mast cell proliferation, maturation, and heparin synthesis by the ratc-kit ligand, stem cell factor.Proc Natl Acad Sci U S A. 1991;88:6382–6386.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Gurish MF, Ghildyal N, McNeil HP, Austen KF, Gillis S, Stevens RL. Differential expression of secretary granule proteases in mouse mast cells exposed to interleukin 3 andc-kit ligand.J Exp Med. 1992;175:1003–1012.CrossRefPubMedGoogle Scholar
  39. 39.
    Ghildyal N, McNeil HP, Stechschulte S, et al. IL-10 induces transcription of the gene for the mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells ofTrichinella spirallis-infected mice.J Immunol. 1992;149:2123–2129.PubMedGoogle Scholar
  40. 40.
    Ghildyal N, McNeil HP, Gurish MF, Austen KF, Stevens RL. Transcriptional regulation of the mucosal mast cell-specific protease gene, MMCP-2, by interleukin 10 and interleukin 3.J Biol Chem. 1992;267:8473–8477.PubMedGoogle Scholar
  41. 41.
    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;151:4266–4273.PubMedGoogle Scholar
  42. 42.
    Friend DS, Ghildyal N, Austen KF, Gurish MF, Matsumoto R, Stevens RL. Mast cells that reside at different locations in the jejunum of mice infected withTrichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype.J Cell Biol. 1996;135:279–290.CrossRefPubMedGoogle Scholar
  43. 43.
    Schwartz LB, Irani AM, Roller K, Castells MC, Schechter M. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells.J Immunol. 1987;138:2611–2615.PubMedGoogle Scholar
  44. 44.
    Valent P, Bevec D, Maurer D, et al. Interleukin 4 promotes expression of mast cell ICAM-1 antigen.Proc Natl Acad Sci U S A. 1991; 88:3339–3342.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sillaber C, Strobl H, Bevec D, et al. IL-4 regulatesc-kit proto-onco- gene product expression in human mast and myeloid progenitor cells.J Immunol. 1991;147:4224–4228.PubMedGoogle Scholar
  46. 46.
    Blank U, Ra C, Miller L, White K, Metzger H, Kinet JP. Complete structure and expression in transfected cells of high affinity IgE receptor.Nature. 1989;337:187–189.CrossRefPubMedGoogle Scholar
  47. 47.
    Lin S, Cicala C, Scharenberg A, Kinet J-P. The atopy-associated FcεRIβ chain gene: the encoded subunit functions as an amplifier of FceRI γ-mediated cell activation signals.Cell. 1996;85:985–995.CrossRefPubMedGoogle Scholar
  48. 48.
    Dombrowicz D, Flamard V, Brigman KK, Koller BH, Kinet J-P. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor A chain gene.Cell. 1993;75:969–976.CrossRefPubMedGoogle Scholar
  49. 49.
    Takai T, Li M, Sylvestre D, Clynes R, Ravetch J. FcR gamma chain deletion results in pleitropic effector cell defects.Cell. 1994;76: 519–529.CrossRefPubMedGoogle Scholar
  50. 50.
    Ravetch JV. Fc receptors: rubor redox.Cell. 1994;78:553–560.CrossRefPubMedGoogle Scholar
  51. 51.
    Nilsson G, Forsberg K, Bodger MP, et al. Phenotypic characterization of stem cell factor-dependent human foetal liver-derived mast cells.Immunology. 1993;79:325–330.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Banks EM, Coleman JW. A comparative study of peritoneal mast cells from mutant IL-4 deficient and normal mice: evidence that IL-4 is not essential for mast cell development but enhances secretion via control of IgE binding and passive sensitization.Cytokine. 1996;8:190–196.CrossRefPubMedGoogle Scholar
  53. 53.
    Xia H-Z, Du Z, Craig S, et al. Effect of recombinant human IL-4 on tryptase, chymase, and Fcε receptor type I expression in recombinant human stem cell factor-dependent fetal liver-derived human mast cells.J Immunol. 1997;159:2911–2921.PubMedGoogle Scholar
  54. 54.
    Bieber T. Fc epsilon RI on human epidermal Langerhans cells: an old receptor with new structure and functions.Int Arch Allergy Immunol. 1997;113:30–34.CrossRefPubMedGoogle Scholar
  55. 55.
    Terada N, Konno A,Terada Y, et al. IL-4 upregulates FcεRI α-chain messenger RNA in eosinophils.J Allergy Clin Immunol. 1995;96: 1161–1169.CrossRefPubMedGoogle Scholar
  56. 56.
    Yamaguchi M, Lantz CS, Oettgen HC, et al. IgE enhances mouse mast cell FcεRI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions.J Exp Med. 1997;185:663–672.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Hsu C, MacGlasham D Jr. IgE antibody up-regulates high affinity IgE binding on murine bone marrow derived mast cells.Immunol Lett. 1996;52:129–134.CrossRefPubMedGoogle Scholar
  58. 58.
    Yamaguchi M, Sayama K, Yano K, et al. IgE enhances Fce receptor 1 expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cells; synergistic effect of IL-4 and IgE on human mast cell Fce receptor 1 expression and mediator release.J Immunol. 1999;162:5455–5465.PubMedGoogle Scholar
  59. 59.
    Daëron M, Latour S, Malbec O, et al. The same tyrosine-based inhibition motif, in the intracytoplasmic domain of FcγRII, regulates negatively BCR-,TCR-, and FcR-dependent cell activation.Immunity. 1995;3:635–646.CrossRefPubMedGoogle Scholar
  60. 60.
    Daëron M, Malbec O, Latour S, Arock M, Fridman WH. Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors.J Clin Invest. 1995;95:577–585.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV. Augmented humoral and anaphylactic responses in FcγRII-deficient mice.Nature. 1996;379:346–349.CrossRefPubMedGoogle Scholar
  62. 62.
    Van den Herik-Oudijk IE, Westerdaal NAC, Henriquez NV, Capel PJA, Van de Winkel JGJ. Functional analysis of human FcγRII (CD32) isoforms expressed in B lymphocytes.J Immunol. 1994; 152:574–585.Google Scholar
  63. 63.
    McNiece IK, Stewart FM, Deacon DM, et al. Detection of a human CFC with a high proliferative potential.Blood. 1989;74:609–612.PubMedGoogle Scholar
  64. 64.
    Nakahata T, Ogawa M. Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors.J Clin Invest. 1982;70: 1324–1328.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Sutherland HJ, Eaves CJ, Eaves AC, Dragowska W, Lansdorp PM. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro.Blood. 1989; 74:1563–1570.PubMedGoogle Scholar
  66. 66.
    Ploemacher RE, Van der Sluijs JP, Voerman JS, Brons NH. An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse.Blood. 1989;74:2755–2763.PubMedGoogle Scholar
  67. 67.
    Larochelle A, Vormoor J, Hanenberg H, et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy.Nat Med. 1996;2:1329–1337.CrossRefPubMedGoogle Scholar
  68. 68.
    Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice.Proc Natl Acad Sci U S A. 1997;94: 5320–5325.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Gan OI, Murdoch B, Larochelle A, Dick JE. Differential maintenance of primitive human SCID-repopulating cells, clonogenic progenitors, and long-term culture-initiating cells after incubation on human bone marrow stromal cells.Blood. 1997;90:641–650.PubMedGoogle Scholar
  70. 70.
    Wang JC, Doedens M, Dick JE. Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay.Blood. 1997;89:3919–3924.PubMedGoogle Scholar
  71. 71.
    Shultz LD, Schweitzer PA, Christianson SW, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.J Immunol. 1995;154:180–191.PubMedGoogle Scholar
  72. 72.
    Xu M, Tsuji K, Mukouyama Y, et al. Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad- mesonephros-derived stromal cells.Blood. 1998;192:2032–2040.Google Scholar
  73. 73.
    Ueda T, Tsuji K, Yoshino H, et al. Expansion of human NOD/ SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor.J Clin Invest. 2000;105:1013–1021.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Ueda T, Yoshino H, Kobayashi K, et al. Hematopoietic repopulating ability of cord blood CD34(+) cells in NOD/Shi-scid mice.Stem Cells. 2000;18:204–213.CrossRefPubMedGoogle Scholar
  75. 75.
    Yoshino H, Ueda T, Kawahata M, et al. Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice.Bone Marrow Transplant. 2000;26:1211–1216.CrossRefPubMedGoogle Scholar
  76. 76.
    Nakahata T. Ex vivo expansion of human hematopoietic stem cells.Int J Hematol. 2001;73:6–13.CrossRefPubMedGoogle Scholar
  77. 77.
    Tsai M,Takeishi T, Thompson H, et al. Induction of mast cell proliferation, maturation, and heparin synthesis by the ratc-kit ligand, stem cell factor.Proc Natl Acad Sci USA. 1991;88:6382–6386.CrossRefPubMedGoogle Scholar
  78. 78.
    Iemura A, Tsai M, Ando A, Wershil BK, Galli SJ. Thec-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis.Am J Pathol. 1994:144:321–328.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Galli SJ, Tsai M, Wershil BK, et al. The effects of stem cell factor, the ligand for thec-kit receptor, on mouse and human mast cell development, survival, and function. In: Kitamura Y, Yamamoto S, Galli SJ, Greaves MW, eds.Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function. New York: Raven Press; 1995:1–11.Google Scholar
  80. 80.
    Jacoby W, Cammarata PV, Findlay S, Pincus S. Anaphylaxis in mast cell-deficient mice.J Invest Dermatol. 1984;83:302–304.CrossRefPubMedGoogle Scholar
  81. 81.
    Ha TY, Reed ND, Crowle PK. Immune response potential of mast cell-deficient W/Wv mice.Int Arch Allergy Appl Immunol. 1986;80: 85–94.CrossRefPubMedGoogle Scholar
  82. 82.
    Ha TY, Reed ND. Systemic anaphylaxis in mast cell-deficient mice of W/Wv and Sl/Sld genotypes.Exp Cell Biol. 1987;55:63–68.PubMedGoogle Scholar
  83. 83.
    Takeishi T, Martin TR, Katona IM, Finkelman FD, Galli SJ. Differences in the expression of cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice.J Clin Invest. 1991;88:598–608.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Martin TR, Ando A, Takeishi T, Katona IM, Drazen JM, Galli SJ. Mast cells contribute to the changes in heart rate, but not hypotension or death, associated with active anaphylaxis in mice.J Immunol. 1993;151:367–376.PubMedGoogle Scholar
  85. 85.
    Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet J-P Galli SJ. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and FcγRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis.J Clin Invest. 1997;99:901–914.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Oettgen HC, Martin TR, Wynshaw-Boris A, Deng C, Drazen JM, Leder P. Active anaphylaxis in IgE-deficient mice.Nature. 1994; 370:367–370.CrossRefPubMedGoogle Scholar
  87. 87.
    Hazenbos WLW, Gessner JE, Hofhuis FMA, et al. Impaired IgG- dependent anaphylaxis and arthus reaction in FcγRIII (CD16) deficient mice.Immunity. 1996;5:181–188.CrossRefPubMedGoogle Scholar
  88. 88.
    Echtenacher B, Männel DN, Hültner L. Critical protective role of mast cells in a model of acute septic peritonitis.Nature. 1996;381: 75–77.CrossRefPubMedGoogle Scholar
  89. 89.
    Malaviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α.Nature. 1996;381:77–80.CrossRefPubMedGoogle Scholar
  90. 90.
    Patella V, Bouvet J-P, Marone G. Protein Fv produced during viral hepatitis is a novel activator of human basophils and mast cells.J Immunol. 1993;151:5685–5698.PubMedGoogle Scholar
  91. 91.
    Marone G, Casolaro V, Patella V, Florio G, Triggiani M. Molecular and cellular biology of mast cells and basophils.Int Arch Allergy Immunol. 1997;114:207–217.CrossRefPubMedGoogle Scholar
  92. 92.
    Marone G. Asthma: recent advances.Immunol Today. 1998;19:5–9.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  1. 1.Department of PediatricsKyoto UniversitySakyo-Ku, Kyoto CityJapan
  2. 2.Department of PediatricsSchool of Medicine, Tokyo Medical and Dental UniversityTokyoJapan

Personalised recommendations