Skip to main content
SpringerLink
Log in

Mast Cells: Effector Cells of Anaphylaxis

  • Chapter
  • First Online:
Anaphylaxis and Hypersensitivity Reactions

Abstract

Mast cells are derived from hematopoietic progenitors, which complete their maturation in peripheral tissues. Mast cells are particularly abundant in tissues exposed to the environment, such as the skin, airways, and gastrointestinal tract. Mast cells can be activated to secrete a wide spectrum of mediators, such as histamine and other stored mediators; lipid mediators such as cysteinyl leukotrienes and prostaglandins; and many cytokines, chemokines, and growth factors. IgE-dependent activation of mast cells and basophils and the rapid release of mediators by these cells represent the primary effector mechanisms responsible for the acute manifestations of allergen-induced anaphylaxis in humans. This chapter reviews the basic biology of mast cells, and describes methods for characterizing the functions of mast cells in vivo. We will particularly emphasize the results of studies designed to assess the importance of mast cells in mouse models of active and passive systemic anaphylaxis, and will briefly describe some approaches that are being used to therapeutically target IgE-dependent activation of mast cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med. 1991;324:1785–1790.

    PubMed  CAS  Google Scholar 

  2. Galli SJ. Pathogenesis and management of anaphylaxis: current status and future challenges. J Allergy Clin Immunol. 2005;115:571–574.

    PubMed  Google Scholar 

  3. Sampson HA, Munoz-Furlong A, Bock SA, et al. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 2005;115:584–591.

    PubMed  Google Scholar 

  4. Simons FE. 9. Anaphylaxis. J Allergy Clin Immunol. 2008;121:S402–407; quiz S420.

    PubMed  CAS  Google Scholar 

  5. Finkelman FD. Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol. 2007;120:506–515; quiz 516–507.

    PubMed  CAS  Google Scholar 

  6. Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. 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.

    PubMed  CAS  Google Scholar 

  7. Strait RT, Morris SC, Yang M, Qu XW, Finkelman FD. Pathways of anaphylaxis in the mouse. J Allergy Clin Immunol. 2002;109:658–668.

    PubMed  CAS  Google Scholar 

  8. Tsujimura Y, Obata K, Mukai K, et al. Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis. Immunity. 2008;28:581–589.

    PubMed  CAS  Google Scholar 

  9. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report – Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391–397.

    PubMed  Google Scholar 

  10. Simons FE, Frew AJ, Ansotegui IJ, et al. Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol. 2007;120:S2–24.

    PubMed  CAS  Google Scholar 

  11. Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–786.

    PubMed  CAS  Google Scholar 

  12. Brown SG, Blackman KE, Heddle RJ. Can serum mast cell tryptase help diagnose anaphylaxis? Emerg Med Australas. 2004;16:120–124.

    PubMed  Google Scholar 

  13. Levy JH. Biomarkers in the diagnosis of anaphylaxis: making nature disclose her mysteries. Clin Exp Allergy. 2009;39:5–7.

    PubMed  CAS  Google Scholar 

  14. Ono E, Taniguchi M, Mita H, et al. Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis. Clin Exp Allergy. 2009;39:72–80.

    PubMed  CAS  Google Scholar 

  15. Peavy RD, Metcalfe DD. Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:310–315.

    PubMed  CAS  Google Scholar 

  16. Kalesnikoff J, Galli SJ. Anaphylaxis: mechanisms of mast cell activation. Chem Immunol Allergy. 2010;95:45–66.

    Google Scholar 

  17. Kitamura Y. Heterogeneity of mast cells and phenotypic change between subpopulations. Annu Rev Immunol. 1989;7:59–76.

    PubMed  CAS  Google Scholar 

  18. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77:1033–1079.

    PubMed  CAS  Google Scholar 

  19. Kawakami T, Galli SJ. Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol. 2002;2:773–786.

    PubMed  CAS  Google Scholar 

  20. Tsai M, Shih LS, Newlands GF, et al. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J Exp Med. 1991;174:125–131.

    PubMed  CAS  Google Scholar 

  21. Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol. 2008;8:478–486.

    PubMed  CAS  Google Scholar 

  22. Miller HR, Wright SH, Knight PA, Thornton EM. A novel function for transforming growth factor-beta1: upregulation of the expression and the IgE-independent extracellular release of a mucosal mast cell granule-specific beta-chymase, mouse mast cell protease-1. Blood. 1999;93:3473–3486.

    PubMed  CAS  Google Scholar 

  23. Ryan JJ, Kashyap M, Bailey D, et al. Mast cell homeostasis: a fundamental aspect of allergic disease. Crit Rev Immunol. 2007;27:15–32.

    PubMed  CAS  Google Scholar 

  24. Irani AM, Craig SS, DeBlois G, Elson CO, Schechter NM, Schwartz LB. Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. J Immunol. 1987;138:4381–4386.

    PubMed  CAS  Google Scholar 

  25. Bannert N, Farzan M, Friend DS, et al. Human mast cell progenitors can be infected by macrophagetropic human immunodeficiency virus type 1 and retain virus with maturation in vitro. J Virol. 2001;75:10808–10814.

    PubMed  CAS  Google Scholar 

  26. Li Y, Li L, Wadley R, et al. Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4. Blood. 2001;97:3484–3490.

    PubMed  CAS  Google Scholar 

  27. Sundstrom JB, Ellis JE, Hair GA, et al. Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood. 2007;109:5293–5300.

    PubMed  CAS  Google Scholar 

  28. Mekori YA, Metcalfe DD. Mast cells in innate immunity. Immunol Rev. 2000;173:131–140.

    PubMed  CAS  Google Scholar 

  29. Grimbaldeston MA, Metz M, Yu M, Tsai M, Galli SJ. Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses. Curr Opin Immunol. 2006;18:751–760.

    PubMed  CAS  Google Scholar 

  30. Dawicki W, Marshall JS. New and emerging roles for mast cells in host defence. Curr Opin Immunol. 2007;19:31–38.

    PubMed  CAS  Google Scholar 

  31. Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M, Galli SJ. Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev. 2007;217:304–328.

    PubMed  CAS  Google Scholar 

  32. Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol. 2008;9:1215–1223.

    PubMed  CAS  Google Scholar 

  33. Blank U, Rivera J. The ins and outs of IgE-dependent mast-cell exocytosis. Trends Immunol. 2004;25:266–273.

    PubMed  CAS  Google Scholar 

  34. Galli SJ, Nakae S, Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol. 2005;6:135–42.

    PubMed  CAS  Google Scholar 

  35. Sayed BA, Brown MA. Mast cells as modulators of T-cell responses. Immunol Rev. 2007;217:53–64.

    PubMed  CAS  Google Scholar 

  36. Theoharides TC, Kempuraj D, Tagen M, Conti P, Kalogeromitros D. Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev. 2007;217:65–78.

    PubMed  CAS  Google Scholar 

  37. Wastling JM, Knight P, Ure J, et al. Histochemical and ultrastructural modification of mucosal mast cell granules in parasitized mice lacking the beta-chymase, mouse mast cell protease-1. Am J Pathol. 1998;153:491–504.

    PubMed  CAS  Google Scholar 

  38. Knight PA, Wright SH, Lawrence CE, Paterson YY, Miller HR. Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1. J. Exp. Med. 2000;192:1849–1856.

    PubMed  CAS  Google Scholar 

  39. Lawrence CE, Paterson YY, Wright SH, Knight PA, Miller HR. Mouse mast cell protease-1 is required for the enteropathy induced by gastrointestinal helminth infection in the mouse. Gastroenterology. 2004;127:155–165.

    PubMed  CAS  Google Scholar 

  40. Tchougounova E, Pejler G, Abrink M. The chymase, mouse mast cell protease 4, constitutes the major chymotrypsin-like activity in peritoneum and ear tissue. A role for mouse mast cell protease 4 in thrombin regulation and fibronectin turnover. J Exp Med. 2003;198:423–431.

    PubMed  CAS  Google Scholar 

  41. Magnusson SE, Pejler G, Kleinau S, Abrink M. Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis. FASEB J. 2009;23:875–882.

    PubMed  CAS  Google Scholar 

  42. Abonia JP, Friend DS, Austen WG Jr, et al. Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle. J Immunol. 2005;174:7285–7291.

    PubMed  CAS  Google Scholar 

  43. Thakurdas SM, Melicoff E, Sansores-Garcia L, et al. The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective role in bacterial infections. J Biol Chem. 2007;282:20809–20815.

    PubMed  CAS  Google Scholar 

  44. Shin K, Watts GF, Oettgen HC, et al. Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection. J Immunol. 2008;180:4885–4891.

    PubMed  CAS  Google Scholar 

  45. McNeil HP, Shin K, Campbell IK, et al. The mouse mast cell-restricted tetramer-forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis. Arthritis Rheum. 2008;58:2338–2346.

    PubMed  Google Scholar 

  46. Feyerabend TB, Hausser H, Tietz A, et al. Loss of histochemical identity in mast cells lacking carboxypeptidase A. Mol Cell Biol. 2005;25:6199–6210.

    PubMed  CAS  Google Scholar 

  47. Schneider LA, Schlenner SM, Feyerabend TB, Wunderlin M, Rodewald HR. Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin. J Exp Med. 2007;204:2629–2639.

    PubMed  CAS  Google Scholar 

  48. Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978;52:447–452.

    PubMed  CAS  Google Scholar 

  49. Lyon MF, Glenister PH. A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice. Genet Res. 1982;39:315–322.

    PubMed  CAS  Google Scholar 

  50. 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. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J Exp Med. 1985;162:1025–1043.

    PubMed  CAS  Google Scholar 

  51. Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ. Mast cell-deficient W-sash c-kit mutant Kit W−sh/W−sh mice as a model for investigating mast cell biology in vivo. Am J Pathol. 2005;167:835–848.

    PubMed  CAS  Google Scholar 

  52. Wolters PJ, Mallen-St Clair J, Lewis CC, et al. Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW-sh/KitW-sh sash mice. Clin Exp Allergy. 2005;35:82–88.

    PubMed  CAS  Google Scholar 

  53. Galli SJ, Zsebo KM, Geissler EN. The kit ligand, stem cell factor. Adv Immunol. 1994;55:1–96.

    PubMed  CAS  Google Scholar 

  54. Duttlinger R, Manova K, Chu TY, et al. W-sash affects positive and negative elements controlling c-kit expression: ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis. Development. 1993;118:705–717.

    PubMed  CAS  Google Scholar 

  55. Nagle DL, Kozak CA, Mano H, Chapman VM, Bucan M. Physical mapping of the Tec and Gabrb1 loci reveals that the Wsh mutation on mouse chromosome 5 is associated with an inversion. Hum Mol Genet. 1995;4:2073–2079.

    PubMed  CAS  Google Scholar 

  56. Berrozpe G, Timokhina I, Yukl S, et al. The Wsh, W57, and Ph Kit expression mutations define tissue-specific control elements located between -23 and -154 kb upstream of Kit. Blood. 1999;94:2658–2666.

    PubMed  CAS  Google Scholar 

  57. Nigrovic PA, Gray DH, Jones T, et al. Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol. 2008;173:1693–1701.

    PubMed  CAS  Google Scholar 

  58. Tsai M, Wedemeyer J, Ganiatsas S, Tam SY, Zon LI, Galli SJ. In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo. Proc Natl Acad Sci USA. 2000;97:9186–9190.

    PubMed  CAS  Google Scholar 

  59. Metz M, Piliponsky AM, Chen CC, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006;313:526–530.

    PubMed  CAS  Google Scholar 

  60. Scholten J, Hartmann K, Gerbaulet A, et al. Mast cell-specific Cre/loxP-mediated recombination in vivo. Transgenic Res. 2008;17:307–315.

    PubMed  CAS  Google Scholar 

  61. Musch W, Wege AK, Mannel DN, Hehlgans T. Generation and characterization of alpha-chymase-Cre transgenic mice. Genesis. 2008;46:163–166.

    PubMed  Google Scholar 

  62. Feyerabend TB, Terszowski G, Tietz A, et al. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity. 2009;30:67–79.

    PubMed  CAS  Google Scholar 

  63. Lantz CS, Yamaguchi M, Oettgen HC, et al. IgE regulates mouse basophil Fc epsilon RI expression in vivo. J Immunol. 1997;158:2517–2521.

    PubMed  CAS  Google Scholar 

  64. Sullivan BM, Locksley RM. Basophils: a nonredundant contributor to host immunity. Immunity. 2009;30:12–20.

    PubMed  CAS  Google Scholar 

  65. Galli SJ, Franco CB. Basophils are back! Immunity. 2008;28:495–497.

    PubMed  CAS  Google Scholar 

  66. Hedin H, Richter W, Messmer K, Renck H, Ljungstrom KG, Laubenthal H. Incidence, pathomechanism and prevention of dextran-induced anaphylactoid//anaphylactic reactions in man. Dev Biol Stand. 1980;48:179–189.

    PubMed  CAS  Google Scholar 

  67. Bergamaschini L, Mannucci PM, Federici AB, Coppola R, Guzzoni S, Agostoni A. Posttransfusion anaphylactic reactions in a patient with severe von Willebrand disease: role of complement and alloantibodies to von Willebrand factor. J Lab Clin Med. 1995;125:348–355.

    PubMed  CAS  Google Scholar 

  68. Cheifetz A, Smedley M, Martin S, et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol. 2003;98:1315–1324.

    PubMed  CAS  Google Scholar 

  69. Umeda Y, Fukumoto Y, Miyauchi T, et al. Anaphylactic shock related to aprotinin induced by anti-aprotinin immunoglobulin G antibody alone; report of a case. Kyobu Geka. 2007;60:69–71.

    PubMed  CAS  Google Scholar 

  70. Fish SC, Donaldson DD, Goldman SJ, Williams CM, Kasaian MT. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol. 2005;174:7716–7724.

    PubMed  CAS  Google Scholar 

  71. Martin TR, Galli SJ, Katona IM, Drazen JM. Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice. J Clin Invest. 1989;83:1375–1383.

    PubMed  CAS  Google Scholar 

  72. Takeishi T, Martin TR, Katona IM, Finkelman FD, Galli SJ. Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. Mast cells are not required for the cardiopulmonary changes associated with certain fatal anaphylactic responses. J Clin Invest. 1991;88:598–608.

    PubMed  CAS  Google Scholar 

  73. Martin TR, Takeishi T, Katz HR, Austen KF, Drazen JM, Galli SJ. Mast cell activation enhances airway responsiveness to methacholine in the mouse. J Clin Invest. 1993;91:1176–1182.

    PubMed  CAS  Google Scholar 

  74. Ando A, Martin TR, Galli SJ. Effects of chronic treatment with the c-kit ligand, stem cell factor, on immunoglobulin E-dependent anaphylaxis in mice. Genetically mast cell-deficient Sl/Sld mice acquire anaphylactic responsiveness, but the congenic normal mice do not exhibit augmented responses. J Clin Invest. 1993;92:1639–1649.

    PubMed  CAS  Google Scholar 

  75. Dombrowicz D, Flamand V, Miyajima I, Ravetch JV, Galli SJ, Kinet JP. Absence of Fc epsilonRI alpha chain results in upregulation of Fc gammaRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between Fc epsilonRI and Fc gammaRIII for limiting amounts of FcR beta and gamma chains. J Clin Invest. 1997;99:915–925.

    PubMed  CAS  Google Scholar 

  76. Hua X, Kovarova M, Chason KD, Nguyen M, Koller BH, Tilley SL. Enhanced mast cell activation in mice deficient in the A2b adenosine receptor. J Exp Med. 2007;204:117–128.

    PubMed  CAS  Google Scholar 

  77. Olivera A, Mizugishi K, Tikhonova A, et al. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity. 2007;26:287–297.

    PubMed  CAS  Google Scholar 

  78. Gri G, Piconese S, Frossi B, et al. CD4  +  CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity. 2008;29:771–781.

    PubMed  CAS  Google Scholar 

  79. Charles N, Watford WT, Ramos HL, et al. Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity. 2009;30:533–543.

    PubMed  CAS  Google Scholar 

  80. Schneider E, Petit-Bertron AF, Bricard R, et al. IL-33 activates unprimed murine basophils directly in vitro and induces their in vivo expansion indirectly by promoting hematopoietic growth factor production. J Immunol. 2009;183:3591–3597.

    PubMed  CAS  Google Scholar 

  81. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63:226–232.

    PubMed  CAS  Google Scholar 

  82. Bonadonna P, Perbellini O, Passalacqua G, et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol. 2009;123:680–686.

    PubMed  CAS  Google Scholar 

  83. Metcalfe DD, Schwartz LB. Assessing anaphylactic risk? Consider mast cell clonality. J Allergy Clin Immunol. 2009;123:687–688.

    PubMed  Google Scholar 

  84. Ring J, Darsow U. Idiopathic anaphylaxis. Curr Allergy Asthma Rep. 2002;2:40–45.

    PubMed  Google Scholar 

  85. Iwaki S, Spicka J, Tkaczyk C, et al. Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells. Cell Signal. 2008;20:195–205.

    PubMed  CAS  Google Scholar 

  86. Rivera J, Proia RL, Olivera A. The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat Rev Immunol. 2008;8:753–763.

    PubMed  CAS  Google Scholar 

  87. Ryan JJ, Spiegel S. The role of sphingosine-1-phosphate and its receptors in asthma. Drug News Perspect. 2008;21:89–96.

    PubMed  CAS  Google Scholar 

  88. Oskeritzian CA, Alvarez SE, Hait NC, Price MM, Milstien S, Spiegel S. Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions. Blood. 2008;111:4193–4200.

    PubMed  CAS  Google Scholar 

  89. Takizawa F, Adamczewski M, Kinet JP. Identification of the low affinity receptor for immunoglobulin E on mouse mast cells and macrophages as Fc gamma RII and Fc gamma RIII. J Exp Med. 1992;176:469–475.

    PubMed  CAS  Google Scholar 

  90. Ujike A, Ishikawa Y, Ono M, et al. Modulation of immunoglobulin (Ig)E-mediated systemic anaphylaxis by low-affinity Fc receptors for IgG. J Exp Med. 1999;189:1573–1579.

    PubMed  CAS  Google Scholar 

  91. Wershil BK, Mekori YA, Murakami T, Galli SJ. 125I-fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin. Demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells. J Immunol. 1987;139:2605–2614.

    PubMed  CAS  Google Scholar 

  92. Wershil BK, Wang ZS, Gordon JR, Galli SJ. Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha. J Clin Invest. 1991;87:446–453.

    PubMed  CAS  Google Scholar 

  93. Gordon JR, Galli SJ. Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha. J Exp Med. 1994;180:2027–2037.

    PubMed  CAS  Google Scholar 

  94. Wershil BK, Furuta GT, Wang ZS, Galli SJ. Mast cell-dependent neutrophil and mononuclear cell recruitment in immunoglobulin E-induced gastric reactions in mice. Gastroenterology. 1996;110:1482–1490.

    PubMed  CAS  Google Scholar 

  95. Furuta GT, Schmidt-Choudhury A, Wang MY, et al. Mast cell-dependent tumor necrosis factor alpha production participates in allergic gastric inflammation in mice. Gastroenterology. 1997;113:1560–1569.

    PubMed  CAS  Google Scholar 

  96. Jawdat DM, Albert EJ, Rowden G, Haidl ID, Marshall JS. IgE-mediated mast cell activation induces Langerhans cell migration in vivo. J Immunol. 2004;173:5275–5282.

    PubMed  CAS  Google Scholar 

  97. Silva SR, Casabuono A, Jacysyn JF, et al. Sialic acid residues are essential for the anaphylactic activity of murine IgG1 antibodies. J Immunol. 2008;181:8308–8314.

    PubMed  CAS  Google Scholar 

  98. Latour S, Bonnerot C, Fridman WH, Daeron M. Induction of tumor necrosis factor-alpha production by mast cells via Fc gamma R. Role of the Fc gamma RIII gamma subunit. J Immunol. 1992;149:2155–2162.

    PubMed  CAS  Google Scholar 

  99. Arimura A, Nagata M, Takeuchi M, Watanabe A, Nakamura K, Harada M. Active and passive cutaneous anaphylaxis in WBB6F1 mouse, a mast cell-deficient strain. Immunol Invest. 1990;19:227–233.

    PubMed  CAS  Google Scholar 

  100. Hazenbos WL, Gessner JE, Hofhuis FM, et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity. 1996;5:181–188.

    PubMed  CAS  Google Scholar 

  101. Nagasaka A, Matsue H, Matsushima H, et al. Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells. Eur J Immunol. 2008;38:489–499.

    PubMed  CAS  Google Scholar 

  102. Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell. 1993;75:969–976.

    PubMed  CAS  Google Scholar 

  103. Katz HR. Inhibition of pathologic inflammation by leukocyte Ig-like receptor B4 and related inhibitory receptors. Immunol Rev. 2007;217:222–230.

    PubMed  CAS  Google Scholar 

  104. Daheshia M, Friend DS, Grusby MJ, Austen KF, Katz HR. Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice. J Exp Med. 2001;194:227–234.

    PubMed  CAS  Google Scholar 

  105. Zabel BA, Nakae S, Zuniga L, et al. Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis. J Exp Med. 2008;205:2207–2220.

    PubMed  CAS  Google Scholar 

  106. Maekawa A, Austen KF, Kanaoka Y. Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses. J Biol Chem. 2002;277:20820–20824.

    PubMed  CAS  Google Scholar 

  107. Jacoby W, Cammarata PV, Findlay S, Pincus SH. Anaphylaxis in mast cell-deficient mice. J Invest Dermatol. 1984;83:302–304.

    PubMed  CAS  Google Scholar 

  108. 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.

    PubMed  CAS  Google Scholar 

  109. 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.

    PubMed  CAS  Google Scholar 

  110. 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.

    PubMed  CAS  Google Scholar 

  111. Kimura S, Nagata M, Takeuchi M, Takano K, Harada M. Anti-granulocyte antibody suppression of active and passive anaphylactic shock in WBB6F1-W/Wv mice. Cell Mol Life Sci. 1997;53:663–666.

    PubMed  CAS  Google Scholar 

  112. Cara DC, Ebbert KV, McCafferty DM. Mast cell-independent mechanisms of immediate hypersensitivity: a role for platelets. J Immunol. 2004;172:4964–4971.

    PubMed  CAS  Google Scholar 

  113. Choi IH, Shin YM, Park JS, et al. Immunoglobulin E-dependent active fatal anaphylaxis in mast cell-deficient mice. J Exp Med. 1998;188:1587–1592.

    PubMed  CAS  Google Scholar 

  114. Choi IW, Kim YS, Kim DK, et al. Platelet-activating factor-mediated NF-kappaB dependency of a late anaphylactic reaction. J Exp Med. 2003;198:145–151.

    PubMed  CAS  Google Scholar 

  115. Park JS, Choi IH, Lee DG, et al. Anti-IL-4 monoclonal antibody prevents antibiotics-induced active fatal anaphylaxis. J Immunol. 1997;158:5002–5006.

    PubMed  CAS  Google Scholar 

  116. Arase N, Arase H, Hirano S, Yokosuka T, Sakurai D, Saito T. IgE-mediated activation of NK cells through Fc gamma RIII. J Immunol. 2003;170:3054–3058.

    PubMed  CAS  Google Scholar 

  117. Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107:191–193.

    PubMed  CAS  Google Scholar 

  118. Sicherer SH, Sampson HA. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med. 2009;60:261–277.

    PubMed  CAS  Google Scholar 

  119. Leung DY, Sampson HA, Yunginger JW, et al. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med. 2003;348:986–993.

    PubMed  CAS  Google Scholar 

  120. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380–384.

    PubMed  CAS  Google Scholar 

  121. Sun J, Arias K, Alvarez D, et al. Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses. J Immunol. 2007;179:6696–6703.

    PubMed  CAS  Google Scholar 

  122. Khodoun M, Strait R, Orekov T, et al. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009;123:342–351.

    PubMed  CAS  Google Scholar 

  123. Smith PL, Kagey-Sobotka A, Bleecker ER, et al. Physiologic manifestations of human anaphylaxis. J Clin Invest. 1980;66:1072–1080.

    PubMed  CAS  Google Scholar 

  124. van der Linden PW, Hack CE, Kerckhaert JA, Struyvenberg A, van der Zwan JC. Preliminary report: complement activation in wasp-sting anaphylaxis. Lancet. 1990;336:904–906.

    PubMed  Google Scholar 

  125. Perdue MH, Masson S, Wershil BK, Galli SJ. Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation. J Clin Invest. 1991;87:687–693.

    PubMed  CAS  Google Scholar 

  126. Brandt EB, Strait RT, Hershko D, et al. Mast cells are required for experimental oral allergen-induced diarrhea. J Clin Invest. 2003;112:1666–1677.

    PubMed  CAS  Google Scholar 

  127. Forbes EE, Groschwitz K, Abonia JP, et al. IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med. 2008;205:897–913.

    PubMed  CAS  Google Scholar 

  128. Hauber HP, Bergeron C, Hamid Q. IL-9 in allergic inflammation. Int Arch Allergy Immunol. 2004;134:79–87.

    PubMed  CAS  Google Scholar 

  129. Redegeld FA, van der Heijden MW, Kool M, et al. Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses. Nat Med. 2002;8:694–701.

    PubMed  CAS  Google Scholar 

  130. Kraneveld AD, Kool M, van Houwelingen AH, et al. Elicitation of allergic asthma by immunoglobulin free light chains. Proc Natl Acad Sci USA. 2005;102:1578–1583.

    PubMed  CAS  Google Scholar 

  131. Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113:832–836.

    PubMed  CAS  Google Scholar 

  132. De Carolis C, Perricone R, De Sanctis G, Fontana L. Complement activation by Hymenoptera venom allergenic extracts. J Allergy Clin Immunol. 1982;70:219–220.

    PubMed  Google Scholar 

  133. von Zabern I, Przyklenk H, Nolte R, Vogt W. Effect of different penicillin derivatives on complement components in human serum. Int Arch Allergy Appl Immunol. 1984;75:164–172.

    Google Scholar 

  134. Erdei A, Andrasfalvy M, Peterfy H, Toth G, Pecht I. Regulation of mast cell activation by complement-derived peptides. Immunol Lett. 2004;92:39–42.

    PubMed  CAS  Google Scholar 

  135. Boyce JA. Successful treatment of cold-induced urticaria/anaphylaxis with anti-IgE. J Allergy Clin Immunol. 2006;117:1415–1418.

    PubMed  CAS  Google Scholar 

  136. MacGlashan DW Jr, Bochner BS, Adelman DC, et al. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol. 1997;158:1438–1445.

    PubMed  CAS  Google Scholar 

  137. Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S. Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol. 2004;114:527–530.

    PubMed  CAS  Google Scholar 

  138. Matsuda K, Piliponky AM, Nakae S, Kawakami T, Tsai M, Galli SJ. IgE enhances human mast cell survival and chemokine production: IL-4 augments the secretory response. J Allergy Clin Immunol. 2005;116:1357–1363.

    PubMed  CAS  Google Scholar 

  139. Asai K, Kitaura J, Kawakami Y, et al. Regulation of mast cell survival by IgE. Immunity. 2001;14:791–800.

    PubMed  CAS  Google Scholar 

  140. 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;14:801–811.

    PubMed  CAS  Google Scholar 

  141. 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 FcepsilonRI. Proc Natl Acad Sci USA. 2003;100:12911–12916.

    PubMed  CAS  Google Scholar 

  142. 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;105:2059–2065.

    PubMed  CAS  Google Scholar 

  143. Zhu D, Kepley CL, Zhang K, Terada T, Yamada T, Saxon A. A chimeric human-cat fusion protein blocks cat-induced allergy. Nat Med. 2005;11:446–449.

    PubMed  CAS  Google Scholar 

  144. Kalesnikoff J, Galli SJ. Nipping cat allergy with fusion proteins. Nat Med. 2005;11:381–382.

    PubMed  CAS  Google Scholar 

  145. Mertsching E, Bafetti L, Hess H, et al. A mouse Fcgamma-Fcepsilon protein that inhibits mast cells through activation of FcgammaRIIB, SH2 domain-containing inositol phosphatase 1, and SH2 domain-containing protein tyrosine phosphatases. J Allergy Clin Immunol. 2008;121:441–447 e445.

    PubMed  CAS  Google Scholar 

  146. Bachelet I, Munitz A, Levi-Schaffer F. Abrogation of allergic reactions by a bispecific antibody fragment linking IgE to CD300a. J Allergy Clin Immunol. 2006;117:1314–1320.

    PubMed  CAS  Google Scholar 

  147. Ong CJ, Ming-Lum A, Nodwell M, et al. Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells. Blood. 2007;110:1942–1949.

    PubMed  CAS  Google Scholar 

  148. Zhang K, Kepley CL, Terada T, Zhu D, Perez H, Saxon A. Inhibition of allergen-specific IgE reactivity by a human Ig Fcgamma-Fcepsilon bifunctional fusion protein. J Allergy Clin Immunol. 2004;114:321–327.

    PubMed  CAS  Google Scholar 

  149. Kashiwakura J, Yokoi H, Saito H, Okayama Y. T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. J Immunol. 2004;173:5247–5257.

    PubMed  CAS  Google Scholar 

  150. Nakae S, Suto H, Iikura M, et al. Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol. 2006;176:2238–2248.

    PubMed  CAS  Google Scholar 

  151. Castells M. Desensitization for drug allergy. Curr Opin Allergy Clin Immunol. 2006;6:476–481.

    PubMed  CAS  Google Scholar 

  152. MacGlashan D Jr, Lavens-Phillips S, Katsushi M. IgE-mediated desensitization in human basophils and mast cells. Front Biosci. 1998;3:d746–756.

    PubMed  Google Scholar 

  153. MacGlashan D Jr. Desensitization of IgE-mediated IL-4 release from human basophils. J Leukoc Biol. 1998;63:59–67.

    PubMed  CAS  Google Scholar 

  154. Kepley CL. Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels. Int Arch Allergy Immunol. 2005;138:29–39.

    PubMed  CAS  Google Scholar 

  155. Plewako H, Wosinska K, Arvidsson M, et al. Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy. Int Arch Allergy Immunol. 2006;141:346–353.

    PubMed  CAS  Google Scholar 

  156. Nagao M, Hiraguchi Y, Hosoki K, et al. Allergen-induced basophil CD203c expression as a biomarker for rush immunotherapy in patients with Japanese cedar pollinosis. Int Arch Allergy Immunol. 2008;146 Suppl 1:47–53.

    PubMed  CAS  Google Scholar 

  157. MacGlashan D Jr, Vilarino N. Polymerization of actin does not regulate desensitization in human basophils. J Leukoc Biol. 2009;85:627–637.

    PubMed  CAS  Google Scholar 

  158. Ishizaka T, Sterk AR, Daeron M, Becker EL, Ishizaka K. Biochemical analysis of desensitization of mouse mast cells. J Immunol. 1985;135:492–501.

    PubMed  CAS  Google Scholar 

  159. Shalit M, Levi-Schaffer F. Challenge of mast cells with increasing amounts of antigen induces desensitization. Clin Exp Allergy. 1995;25:896–902.

    PubMed  CAS  Google Scholar 

  160. Rubinchik E, Shalit M, Levi-Schaffer F. Responsiveness of human skin mast cells to repeated activation: an in vitro study. Allergy. 1998;53:14–19.

    PubMed  CAS  Google Scholar 

  161. Morales AR, Shah N, Castells M. Antigen-IgE desensitization in signal transducer and activator of transcription 6-deficient mast cells by suboptimal doses of antigen. Ann Allergy Asthma Immunol. 2005;94:575–580.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Stephen J. Galli (Professor of Pathology and of Microbiology and Immunology)

Authors
  1. Mindy Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen J. Galli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen J. Galli .

Editor information

Editors and Affiliations

  1. Harvard Medical School, Ambulatory Center, Brigham and Women’s Hospital, Boyleston Street, Route 9 850, Chestnut Hill, 02467, Massachusetts, USA

    Mariana C. Castells

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Tsai, M., Galli, S.J. (2011). Mast Cells: Effector Cells of Anaphylaxis. In: Castells, M. (eds) Anaphylaxis and Hypersensitivity Reactions. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-951-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-951-2_4

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-950-5

  • Online ISBN: 978-1-60327-951-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation