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Overview of Mast Cells in Human Biology

  • Dean D. MetcalfeEmail author
  • Do-Kyun Kim
  • Ana Olivera
Chapter

Abstract

Mast cells are derived from hematopoietic precursors and as mature cells reside in tissues. Mast cells express receptors that endow their function in innate and acquired immunity. In addition to FcεRI, the high-affinity receptor of IgE, and other immunoglobulin Fc receptors, mast cells express microbial pattern recognition receptors; Toll-like and NOD-like receptors (TLR and NLR); Mas-related G-protein-coupled receptor member X2 (MRGX2) that recognizes cationic neuropeptides, antimicrobial peptides, and insect-venom peptides; and receptors that recognize molecules associated with tissue damage, such as ST2, the IL-33 receptor. Mast cells are thus able to respond to both exogenous and endogenous stimuli with release of histamine and lipid mediators, cytokines, chemokines, growth factors, and proteases. Mast cells are potentially lethal cells (anaphylaxis) or can cause tissue damage if their activation is sustained. Mutations, principally in KIT, the receptor for stem cell factor (SCF), lead to excess mast cell proliferation and mastocytosis.

Keywords

Mast cells Stem cell factor KIT FcεRI Receptors Mediators Mastocytosis 

Abbreviations

5-LO

5-Lipoxygenase

ADGRE2

Adhesion G-protein-coupled receptor type E2

or EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2)

CCL2

CC-motif chemokine ligand 2

CD203c

Ectonucleotide pyrophosphates/phosphodiesterases type 3 (E-NPP3)

CD25

α-Chain of the IL-2 receptor

CD30

Tumor necrosis factor receptor/nerve growth factor receptor superfamily member

CD63

Membrane tetraspanin protein family member

COX

Cyclooxygenase

CTMC

Connective tissue mast cell (rodents)

CysLTs

Cysteinyl leukotrienes

DJ-1

Antioxidant protein DJ-1 or Parkinsonism-associated deglycase (PARK7)

ERK1/2

Extracellular-signal-regulated kinase 1 and 2

FcεRI

High-affinity receptor of IgE

GAB2

GRAB2-associated binding protein 2

GEF

Guanine exchange factor

GPCR

G-protein-coupled receptor

GPR-35

G-protein-coupled receptor 35

GRB2

Growth factor receptor-bound protein 2

IL-2R

IL-2 receptor

JNK

c-Jun N-terminal kinase

KIT

Receptor for stem cell factor

LAT

Linker of activation of T cells

LTB4

Leukotriene B4

LTC4

Leukotriene C4

MAPK

Mitogen-activated protein kinase

MCT

Mast cell tryptase (humans)

MCTC

Mast cells containing tryptase and chymase (humans)

MMC

Mucosal mast cells (rodents)

MRGX2

Mas-related G-protein-coupled receptor member X2

MyD88

Myeloid differentiation primary response 88

NLR

NOD-like receptors

PAF

Platelet-activating factor

PGD2

Prostaglandin D2

PH domain

Pleckstrin homology domain

PI(3,4,5)P3

Phosphatidylinositol-3,4,5,-triphosphate

PI3K

Phosphatidylinositol-3-kinase

PKC

Protein kinase C

PLCγ

Phospholipase C γ

PTB domain

Phosphotyrosine-binding domain

SCF

Stem cell factor

SFK

Src family kinase

SH2 domain

Src homology 2 domain

SHC

Src Homology 2 domain-containing adaptor protein

SOS

Son of Sevenless

ST2

IL-33 receptor

SYK

Spleen tyrosine kinase

TLR

Toll-like receptors

Notes

Acknowledgments

DDM, AO, and D-K Kim are supported by the Division of Intramural Research, NIAID.

References

  1. 1.
    Crivellato E, Travan L, Ribatti D. The phylogenetic profile of mast cells. Methods Mol Biol. 2015;1220:11–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Cavalcante MC, Allodi S, Valente AP, Straus AH, Takahashi HK, Mourao PA, et al. Occurrence of heparin in the invertebrate Styela plicata (Tunicata) is restricted to cell layers facing the outside environment. An ancient role in defense? J Biol Chem. 2000;275(46):36189–96.PubMedCrossRefGoogle Scholar
  3. 3.
    Cavalcante MC, de Andrade LR, Du Bocage Santos-Pinto C, Straus AH, Takahashi HK, Allodi S, et al. Colocalization of heparin and histamine in the intracellular granules of test cells from the invertebrate Styela plicata (Chordata-Tunicata). J Struct Biol. 2002;137(3):313–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Wong GW, Zhuo L, Kimata K, Lam BK, Satoh N, Stevens RL. Ancient origin of mast cells. Biochem Biophys Res Commun. 2014;451(2):314–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Dawicki W, Marshall JS. New and emerging roles for mast cells in host defence. Curr Opin Immunol. 2007;19:31–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Mukai K, Tsai M, Starkl P, Marichal T, Galli SJ. IgE and mast cells in host defense against parasites and venoms. Semin Immunopathol. 2016;38(5):581–603.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Da’as S, Teh EM, Dobson JT, Nasrallah GK, McBride ER, Wang H, et al. Zebrafish mast cells possess an FceRI-like receptor and participate in innate and adaptive immune responses. Dev Comp Immunol. 2011;35(1):125–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Akula S, Mohammadamin S, Hellman L. Fc receptors for immunoglobulins and their appearance during vertebrate evolution. PLoS One. 2014;9(5):e96903.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693–704.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Gilfillan AM, Beaven MA. Regulation of mast cell responses in health and disease. Crit Rev Immunol. 2011;31:475–529.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Rivera J, Fierro NA, Olivera A, Suzuki R. New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol. 2008;98:85–120.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Kim DK, Beaven MA, Metcalfe DD, Olivera A. Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells. J Allergy Clin Immunol. 2018;142(1):195–206 e8.PubMedCrossRefGoogle Scholar
  13. 13.
    Okayama Y, Hagaman DD, Metcalfe DD. A comparison of mediators released or generated by IFN-gamma-treated human mast cells following aggregation of fc gamma RI or fc epsilon RI. J Immunol. 2001;166(7):4705–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Tkaczyk C, Okayama Y, Metcalfe DD, Gilfillan AM. Fcgamma receptors on mast cells: activatory and inhibitory regulation of mediator release. Int Arch Allergy Immunol. 2004;133(3):305–15.PubMedCrossRefGoogle Scholar
  15. 15.
    Tkaczyk C, Okayama Y, Woolhiser MR, Hagaman DD, Gilfillan AM, Metcalfe DD. Activation of human mast cells through the high affinity IgG receptor. Mol Immunol. 2002;38(16–18):1289–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Fong DC, Malbec O, Arock M, Cambier JC, Fridman WH, Daeron M. Selective in vivo recruitment of the phosphatidylinositol phosphatase SHIP by phosphorylated fc gammaRIIB during negative regulation of IgE-dependent mouse mast cell activation. Immunol Lett. 1996;54(2–3):83–91.PubMedCrossRefGoogle Scholar
  17. 17.
    Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, et al. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987;6(11):3341–51.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Qiu FH, Ray P, Brown K, Barker PE, Jhanwar S, Ruddle FH, et al. Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family–oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J. 1988;7(4):1003–11.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Broudy VC. Stem cell factor and hematopoiesis. Blood. 1997;90(4):1345–64.PubMedCrossRefGoogle Scholar
  20. 20.
    Reber L, Da Silva CA, Frossard N. Stem cell factor and its receptor c-kit as targets for inflammatory diseases. Eur J Pharmacol. 2006;533(1–3):327–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Kitamura Y, Oboki K, Ito A. Molecular mechanisms of mast cell development. Immunol Allergy Clin N Am. 2006;26(3):387–405; vCrossRefGoogle Scholar
  22. 22.
    Jensen BM, Akin C, Gilfillan AM. Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders. Br J Pharmacol. 2008;154(8):1572–82.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373(6512):347–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Oiso N, Fukai K, Kawada A, Suzuki T. Piebaldism. J Dermatol. 2013;40(5):330–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A. 1995;92(23):10560–4.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Tran A, Tawbi HA. A potential role for nilotinib in KIT-mutated melanoma. Expert Opin Investig Drugs. 2012;21(6):861–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Ashman LK, Griffith R. Therapeutic targeting of c-KIT in cancer. Expert Opin Investig Drugs. 2013;22(1):103–15.PubMedCrossRefGoogle Scholar
  28. 28.
    Brockow K, Metcalfe DD. Mastocytosis. Chem Immunol Allergy. 2010;95:110–24.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130(2):323–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J. Kit receptor dimerization is driven by bivalent binding of stem cell factor. J Biol Chem. 1997;272(10):6311–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-kit tyrosine kinase. J Biol Chem. 2004;279(30):31655–63.PubMedCrossRefGoogle Scholar
  32. 32.
    Ronnstrand L. Signal transduction via the stem cell factor receptor/c-kit. Cell Mol Life Sci. 2004;61(19–20):2535–48.PubMedCrossRefGoogle Scholar
  33. 33.
    Abram CL, Courtneidge SA. Src family tyrosine kinases and growth factor signaling. Exp Cell Res. 2000;254(1):1–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Arcaro A, Aubert M, Espinosa del Hierro ME, Khanzada UK, Angelidou S, Tetley TD, et al. Critical role for lipid raft-associated Src kinases in activation of PI3K-Akt signalling. Cell Signal. 2007;19(5):1081–92.PubMedCrossRefGoogle Scholar
  35. 35.
    Tan BL, Yazicioglu MN, Ingram D, McCarthy J, Borneo J, Williams DA, et al. Genetic evidence for convergence of c-Kit- and alpha4 integrin-mediated signals on class IA PI-3kinase and the Rac pathway in regulating integrin-directed migration in mast cells. Blood. 2003;101(12):4725–32.PubMedCrossRefGoogle Scholar
  36. 36.
    Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012;66(2):105–43.PubMedCrossRefGoogle Scholar
  37. 37.
    Ehrlich P. Beitrage zur Kenntnis der Anilinfarbungen und ihrer Verwendung in der mikroskopischen Technik. Arch Mikr Anat. 1877;13:263–77.CrossRefGoogle Scholar
  38. 38.
    Ehrlich P. Beitrage zur Theorie und Praxis der histologischen Farbung. Thesis, Leipzig University; 1878.Google Scholar
  39. 39.
    Beaven MA. Our perception of the mast cell from Paul Ehrlich to now. Eur J Immunol. 2009;39:11–25.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Tatemoto K, Nozaki Y, Tsuda R, Konno S, Tomura K, Furuno M, et al. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun. 2006;349:1322–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Kulka M, Sheen CH, Tancowny BP, Grammer LC, Schleimer RP. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology. 2008;123:398–410.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Niyonsaba F, Ushio H, Hara M, Yokoi H, Tominaga M, Takamori K, et al. Antimicrobial peptides human á-defensins and cathelicidin LL-37 induce the secretion of a pruritogenic cytokine IL-31 by human mast cells. J Immunol. 2010;184:3526–34.PubMedCrossRefGoogle Scholar
  43. 43.
    Yu Y, Blokhuis BR, Garssen J, Redegeld FA. Non-IgE mediated mast cell activation. Eur J Pharmacol. 2016;778:33–43.PubMedCrossRefGoogle Scholar
  44. 44.
    McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237–41.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Subramanian H, Gupta K, Ali H. Roles of mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138(3):700–10.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Fujisawa D, Kashiwakura J, Kita H, Kikukawa Y, Fujitani Y, Sasaki-Sakamoto T, et al. Expression of mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J Allergy Clin Immunol. 2014;134(3):622–33.. e9PubMedCrossRefGoogle Scholar
  47. 47.
    Kovalszki A, Weller PF. Eosinophilia in mast cell disease. Immunol Allergy Clin N Am. 2014;34(2):357–64.CrossRefGoogle Scholar
  48. 48.
    Marshall JS, Jawdat DM. Mast cells in innate immunity. J Allergy Clin Immunol. 2004;114(1):21–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Yang S, Liu Y, Lin AA, Cavalli-Sforza LL, Zhao Z, Su B. Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception. Gene. 2005;352:30–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Cox JS. Disodium cromoglycate (FPL 670) (‘Intal’): a specific inhibitor of reaginic antibody-antigen mechanisms. Nature. 1967;216(5122):1328–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Binti Mohd Amir NAS, Mackenzie AE, Jenkins L, Boustani K, Hillier MC, Tsuchiya T, et al. Evidence for the existence of a CXCL17 receptor distinct from GPR35. J Immunol. 2018;201(2):714–24.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Yang Y, Lu JY, Wu X, Summer S, Whoriskey J, Saris C, et al. G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium. Pharmacology. 2010;86(1):1–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Church MK, Gradidge CF. The activity of sodium cromoglycate analogues in human lung in vitro: a comparison with rat passive cutaneous anaphylaxis and clinical efficacy. Br J Pharmacol. 1980;70(2):307–11.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Leung KB, Flint KC, Brostoff J, Hudspith BN, Johnson NM, Lau HY, et al. Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells. Thorax. 1988;43(10):756–61.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Scholz N, Monk KR, Kittel RJ, Langenhan T. Adhesion GPCRs as a putative class of metabotropic Mechanosensors. Handb Exp Pharmacol. 2016;234:221–47.PubMedCrossRefGoogle Scholar
  56. 56.
    Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, et al. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol. 2012;32(8):1408–20.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, et al. Vibratory Urticaria associated with a missense variant in ADGRE2. N Engl J Med. 2016;374(7):656–63.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Makrinioti H, Toussaint M, Jackson DJ, Walton RP, Johnston SL. Role of interleukin 33 in respiratory allergy and asthma. Lancet Respir Med. 2014;2(3):226–37.PubMedCrossRefGoogle Scholar
  59. 59.
    Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16(11):676–89.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Saluja R, Zoltowska A, Ketelaar ME, Nilsson G. IL-33 and Thymic stromal Lymphopoietin in mast cell functions. Eur J Pharmacol. 2016;778:68–76.PubMedCrossRefGoogle Scholar
  61. 61.
    Olivera A, Beaven MA, Metcalfe DD. Mast cells signal their importance in health and disease. J Allergy Clin Immunol. 2018;142:381.PubMedCrossRefGoogle Scholar
  62. 62.
    Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cutting edge: the ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol. 2007;179(4):2051–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Tsuzuki H, Arinobu Y, Miyawaki K, Takaki A, Ota SI, Ota Y, et al. Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes. Immunology. 2017;150(1):64–73.PubMedCrossRefGoogle Scholar
  64. 64.
    Pols MS, Klumperman J. Trafficking and function of the tetraspanin CD63. Exp Cell Res. 2009;315(9):1584–92.PubMedCrossRefGoogle Scholar
  65. 65.
    Sturm EM, Kranzelbinder B, Heinemann A, Groselj-Strele A, Aberer W, Sturm GJ. CD203c-based basophil activation test in allergy diagnosis: characteristics and differences to CD63 upregulation. Cytometry B Clin Cytom. 2010;78(5):308–18.PubMedCrossRefGoogle Scholar
  66. 66.
    Buhring HJ, Streble A, Valent P. The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell activation and allergy diagnosis. Int Arch Allergy Immunol. 2004;133(4):317–29.PubMedCrossRefGoogle Scholar
  67. 67.
    Yano Y, Hayashi Y, Sano K, Shinmaru H, Kuroda Y, Yokozaki H, et al. Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-3 (E-NPP3/CD203c/PD-I beta/B10/gp130RB13-6) in human colon carcinoma. Int J Mol Med. 2003;12(5):763–6.PubMedGoogle Scholar
  68. 68.
    Hauswirth AW, Escribano L, Prados A, Nunez R, Mirkina I, Kneidinger M, et al. CD203c is overexpressed on neoplastic mast cells in systemic mastocytosis and is upregulated upon IgE receptor cross-linking. Int J Immunopathol Pharmacol. 2008;21(4):797–806.PubMedCrossRefGoogle Scholar
  69. 69.
    Perini GF, Pro B. Brentuximab Vedotin in CD30+ lymphomas. Biol Ther. 2013;3:15–23.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Morgado JM, Perbellini O, Johnson RC, Teodosio C, Matito A, Alvarez-Twose I, et al. CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis. Histopathology. 2013;63(6):780–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008;26:453–79.PubMedCrossRefGoogle Scholar
  72. 72.
    Valent P, Cerny-Reiterer S, Herrmann H, Mirkina I, George TI, Sotlar K, et al. Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells. Best Pract Res Clin Haematol. 2010;23(3):369–78.PubMedCrossRefGoogle Scholar
  73. 73.
    Casale TB, Wood D, Richerson HB, Trapp S, Metzger WJ, Zavala D, et al. Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness. J Clin Invest. 1987;79(4):1197–203.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Kaplan AP, Horakova Z, Katz SI. Assessment of tissue fluid histamine levels in patients with urticaria. J Allergy Clin Immunol. 1978;61(6):350–4.PubMedCrossRefGoogle Scholar
  75. 75.
    Granerus G, Lonnqvist B, Wass U. Determination of the histamine metabolite tele-methylimidazoleacetic acid and of creatinine in urine by the same HPLC system. Inflamm Res. 1999;48(2):75–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Friedman BS, Steinberg SC, Meggs WJ, Kaliner MA, Frieri M, Metcalfe DD. Analysis of plasma histamine levels in patients with mast cell disorders. Am J Med. 1989;87(6):649–54.PubMedCrossRefGoogle Scholar
  77. 77.
    Metcalfe DD, Lewis RA, Silbert JE, Rosenberg RD, Wasserman SI, Austen KF. Isolation and characterization of heparin from human lung. J Clin Invest. 1979;64(6):1537–43.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Metcalfe DD, Soter NA, Wasserman SI, Austen KF. Identification of sulfated mucopolysaccharides including heparin in the lesional skin of a patient with mastocytosis. J Invest Dermatol. 1980;74(4):210–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Sucker C, Mansmann G, Steiner S, Gattermann N, Schmitt-Graeff A, Loncar R, et al. Fatal bleeding due to a heparin-like anticoagulant in a 37-year-old woman suffering from systemic mastocytosis. Clin Appl Thromb Hemost. 2008;14(3):360–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Dwyer DF, Barrett NA, Austen KF. Immunological genome project C. expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat Immunol. 2016;17(7):878–87.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Caughey GH. Mast cell proteases as pharmacological targets. Eur J Pharmacol. 2016;778:44–55.PubMedCrossRefGoogle Scholar
  82. 82.
    Tsai M, Starkl P, Marichal T, Galli SJ. Testing the ‘toxin hypothesis of allergy’: mast cells, IgE, and innate and acquired immune responses to venoms. Curr Opin Immunol. 2015;36:80–7.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G. Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol. 2015;126:45–127.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–25.CrossRefGoogle Scholar
  85. 85.
    Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D, 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(3):680–6.CrossRefPubMedGoogle Scholar
  86. 86.
    Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016;48(12):1564–9.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Metcalfe DD, Pawankar R, Ackerman SJ, Akin C, Clayton F, Falcone FH, et al. Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases. World Allergy Organ J. 2016;9:7.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    He A, Shi GP. Mast cell chymase and tryptase as targets for cardiovascular and metabolic diseases. Curr Pharm Des. 2013;19(6):1114–25.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Oskeritzian CA. Mast cells and wound healing. Adv Wound Care (New Rochelle). 2012;1(1):23–8.CrossRefGoogle Scholar
  90. 90.
    Walter M, Sutton RM, Schechter NM. Highly efficient inhibition of human chymase by alpha(2)-macroglobulin. Arch Biochem Biophys. 1999;368(2):276–84.PubMedCrossRefGoogle Scholar
  91. 91.
    Raymond WW, Su S, Makarova A, Wilson TM, Carter MC, Metcalfe DD, et al. Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity. J Immunol. 2009;182(9):5770–7.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Goldstein SM, Kaempfer CE, Kealey JT, Wintroub BU. Human mast cell carboxypeptidase. Purification and characterization. J Clin Invest. 1989;83(5):1630–6.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Fajt ML, Wenzel SE. Mast cells, their subtypes, and relation to asthma phenotypes. Ann Am Thorac Soc. 2013;10(Suppl):S158–64.PubMedCrossRefGoogle Scholar
  94. 94.
    D’Ambrosio C, Akin C, Wu Y, Magnusson MK, Metcalfe DD. Gene expression analysis in mastocytosis reveals a highly consistent profile with candidate molecular markers. J Allergy Clin Immunol. 2003;112(6):1162–70.PubMedCrossRefGoogle Scholar
  95. 95.
    Simons FE, Frew AJ, Ansotegui IJ, Bochner BS, Golden DB, Finkelman FD, et al. Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol. 2007;120(1 Suppl):S2–24.PubMedCrossRefGoogle Scholar
  96. 96.
    Fanning LB, Boyce JA. Lipid mediators and allergic diseases. Ann Allergy Asthma Immunol. 2013;111(3):155–62.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Ravi A, Butterfield J, Weiler CR. Mast cell activation syndrome: improved identification by combined determinations of serum tryptase and 24-hour urine 11beta-prostaglandin2alpha. J Allergy Clin Immunol Pract. 2014;2(6):775–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Kanaoka Y, Boyce JA. Cysteinyl leukotrienes and their receptors; emerging concepts. Allergy Asthma Immunol Res. 2014;6(4):288–95.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Butterfield JH. Increased leukotriene E4 excretion in systemic mastocytosis. Prostaglandins Other Lipid Mediat. 2010;92(1–4):73–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Laboratory of Allergic DiseasesNIAID, NIHBethesdaUSA
  2. 2.Mast Cell Biology Section, Laboratory of Allergic DiseasesNational Institutes of Health (NIH)BethesdaUSA

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