Mast Cells pp 93-119 | Cite as

Mast Cells in Human Health and Disease

  • Erin J. DeBruin
  • Matthew Gold
  • Bernard C. Lo
  • Kimberly Snyder
  • Alissa Cait
  • Nikola Lasic
  • Martin Lopez
  • Kelly M. McNagny
  • Michael R. HughesEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1220)


Mast cells are primarily known for their role in defense against pathogens, particularly bacteria; neutralization of venom toxins; and for triggering allergic responses and anaphylaxis. In addition to these direct effector functions, activated mast cells rapidly recruit other innate and adaptive immune cells and can participate in “tuning” the immune response. In this review we touch briefly on these important functions and then focus on some of the less-appreciated roles of mast cells in human disease including cancer, autoimmune inflammation, organ transplant, and fibrosis. Although it is difficult to formally assign causal roles to mast cells in human disease, we offer a general review of data that correlate the presence and activation of mast cells with exacerbated inflammation and disease progression. Conversely, in some restricted contexts, mast cells may offer protective roles. For example, the presence of mast cells in some malignant or cardiovascular diseases is associated with favorable prognosis. In these cases, specific localization of mast cells within the tissue and whether they express chymase or tryptase (or both) are diagnostically important considerations. Finally, we review experimental animal models that imply a causal role for mast cells in disease and discuss important caveats and controversies of these findings.

Key words

Autoimmune disease Asthma Allergy Cancer Cardiovascular disease Fibrosis Inflammatory bowel disease Mastocytosis Organ transplant Pathogen clearance 


  1. 1.
    Hu Z-Q, Zhao W-H, Shimamura T (2007) Regulation of mast cell development by inflammatory factors. Curr Med Chem 14: 3044–3050PubMedGoogle Scholar
  2. 2.
    Collington SJ, Williams TJ, Weller CL (2011) Mechanisms underlying the localisation of mast cells in tissues. Trends Immunol 32: 478–485PubMedGoogle Scholar
  3. 3.
    Iemura A, Tsai M, Ando A et al (1994) The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol 144:321–328PubMedCentralPubMedGoogle Scholar
  4. 4.
    Orinska Z, Föger N, Huber M et al (2010) I787 provides signals for c-Kit receptor internalization and functionality that control mast cell survival and development. Blood 116:2665–2675PubMedGoogle Scholar
  5. 5.
    Abraham SN, John ALS (2010) Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10:440–452PubMedGoogle Scholar
  6. 6.
    Galli SJ, Borregaard N, Wynn TA (2011) Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol 12:1035–1044PubMedCentralPubMedGoogle Scholar
  7. 7.
    Moon TC, St Laurent CD, Morris KE et al (2009) Advances in mast cell biology: new understanding of heterogeneity and function. Mucosal Immunol 3:111–128PubMedGoogle Scholar
  8. 8.
    Marshall JS (2004) Mast-cell responses to pathogens. Nat Rev Immunol 4:787–799PubMedGoogle Scholar
  9. 9.
    Holgate ST, Hardy C, Robinson C et al (1986) The mast cell as a primary effector cell in the pathogenesis of asthma. J Allergy Clin Immunol 77:274–282PubMedGoogle Scholar
  10. 10.
    Irani AA, Schechter NM, Craig SS et al (1986) Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A 83:4464–4468PubMedCentralPubMedGoogle Scholar
  11. 11.
    Bax HJ, Keeble AH, Gould HJ (2012) Cytokinergic IgE action in mast cell activation. Front Immunol 3:229PubMedCentralPubMedGoogle Scholar
  12. 12.
    Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995PubMedGoogle Scholar
  13. 13.
    Williams CMM, Galli SJ (2000) The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol 105:847–859PubMedGoogle Scholar
  14. 14.
    Theoharides TC, Alysandratos K-D, Angelidou A et al (2012) Mast cells and inflammation. Biochim Biophys Acta 1822:21–33PubMedCentralPubMedGoogle Scholar
  15. 15.
    Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9: 654–659PubMedGoogle Scholar
  16. 16.
    Skokos D, Botros HG, Demeure C et al (2003) Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol 170:3037–3045PubMedGoogle Scholar
  17. 17.
    Pulimood AB, Mathan MM, Mathan VI (1998) Quantitative and ultrastructural analysis of rectal mucosal mast cells in acute infectious diarrhea. Dig Dis Sci 43:2111–2116PubMedGoogle Scholar
  18. 18.
    Matsuo T, Ikura Y, Ohsawa M et al (2003) Mast cell chymase expression in Helicobacter pylori-associated gastritis. Histopathology 43: 538–549PubMedGoogle Scholar
  19. 19.
    Raqib R, Moly PK, Sarker P et al (2003) Persistence of mucosal mast cells and eosinophils in Shigella-infected children. Infect Immun 71:2684–2692PubMedCentralPubMedGoogle Scholar
  20. 20.
    Qadri F, Bhuiyan TR, Dutta KK et al (2004) Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut. Gut 53:62–69PubMedCentralPubMedGoogle Scholar
  21. 21.
    Galli SJ, Nakae S, Tsai M (2005) Mast cells in the development of adaptive immune responses. Nat Immunol 6:135–142PubMedGoogle Scholar
  22. 22.
    Ha TY, Reed ND, Crowle PK (1983) Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice. Infect Immun 41: 445–447PubMedCentralPubMedGoogle Scholar
  23. 23.
    Alizadeh H, Murrell KD (1984) The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice. J Parasitol 70:767PubMedGoogle Scholar
  24. 24.
    Knight PA, Wright SH, Lawrence CE et al (2000) 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 192:1849–1856PubMedCentralPubMedGoogle Scholar
  25. 25.
    Lawrence CE, Paterson YYW, Wright SH et al (2004) Mouse mast cell protease-1 is required for the enteropathy induced by gastrointestinal helminth infection in the mouse. Gastroenterology 127:155–165PubMedGoogle Scholar
  26. 26.
    Woodbury RG, Miller HRP, Huntley JF et al (1984) Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat. Nature 312: 450–452PubMedGoogle Scholar
  27. 27.
    Urban JF, Katona IM, Paul WE et al (1991) Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci U S A 88: 5513–5517PubMedCentralPubMedGoogle Scholar
  28. 28.
    Finkelman FD, Shea-Donohue T, Morris SC et al (2004) Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol Rev 201:139–155PubMedGoogle Scholar
  29. 29.
    McDermott JR, Bartram RE, Knight PA et al (2003) Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci U S A 100:7761–7766PubMedCentralPubMedGoogle Scholar
  30. 30.
    Kitamura Y, Go S, Hatanaka K (1978) Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52: 447–452PubMedGoogle Scholar
  31. 31.
    Maurer M, Kostka SL, Siebenhaar F et al (2006) Skin mast cells control T cell-dependent host defense in Leishmania major infections. FASEB J 20:2460–2467PubMedGoogle Scholar
  32. 32.
    Dudeck A, Suender CA, Kostka SL et al (2011) Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function. Eur J Immunol 41:1883–1893PubMedGoogle Scholar
  33. 33.
    Urban BC, Cordery D, Shafi MJ et al (2006) The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infect Immun 74:6700–6706PubMedCentralPubMedGoogle Scholar
  34. 34.
    Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5:722–735PubMedGoogle Scholar
  35. 35.
    Guermonprez P, Helft J, Claser C et al (2013) Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat Med 19: 730–738PubMedCentralPubMedGoogle Scholar
  36. 36.
    Echtenacher B, Männel DN, Hültner L (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381:75–77PubMedGoogle Scholar
  37. 37.
    Lin T-J, Garduno R, Boudreau RTM et al (2002) Pseudomonas aeruginosa activates human mast cells to induce neutrophil transendothelial migration via mast cell-derived IL-1α and β. J Immunol 169:4522–4530PubMedGoogle Scholar
  38. 38.
    Malaviya R, Ikeda T, Ross E et al (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α. Nature 381:77–80PubMedGoogle Scholar
  39. 39.
    Malaviya R, Abraham SN (2000) Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis. J Leukoc Biol 67:841–846PubMedGoogle Scholar
  40. 40.
    Huang C, Friend DS, Qiu W-T et al (1998) Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6. J Immunol 160:1910–1919PubMedGoogle Scholar
  41. 41.
    Tani K, Ogushi F, Kido H et al (2000) Chymase is a potent chemoattractant for human monocytes and neutrophils. J Leukoc Biol 67: 585–589PubMedGoogle Scholar
  42. 42.
    Huang C, Sanctis GTD, O’Brien PJ et al (2001) Evaluation of the substrate specificity of human mast cell tryptase βI and demonstration of its importance in bacterial infections of the lung. J Biol Chem 276:26276–26284PubMedGoogle Scholar
  43. 43.
    Nardo AD, Vitiello A, Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170:2274–2278PubMedGoogle Scholar
  44. 44.
    Abel J, Goldmann O, Ziegler C et al (2011) Staphylococcus aureus evades the extracellular antimicrobial activity of mast cells by promoting its own uptake. J Innate Immun 3:495–507PubMedGoogle Scholar
  45. 45.
    Liu F-T, Goodarzi H, Chen H-Y (2011) IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol 41:298–310PubMedGoogle Scholar
  46. 46.
    Muñoz S, Rivas-Santiago B, Enciso JA (2009) Mycobacterium tuberculosis entry into mast cells through cholesterol-rich membrane microdomains. Scand J Immunol 70:256–263PubMedGoogle Scholar
  47. 47.
    Mañes S, del Real G, Martínez-A C (2003) Pathogens: raft hijackers. Nat Rev Immunol 3:557–568PubMedGoogle Scholar
  48. 48.
    Dawicki W, Jawdat DW, Xu N et al (2010) Mast cells, histamine, and IL-6 regulate the selective influx of dendritic cell subsets into an inflamed lymph node. J Immunol 184: 2116–2123PubMedGoogle Scholar
  49. 49.
    Gauchat J-F, Henchoz S, Mazzei G et al (1993) Induction of human IgE synthesis in B cells by mast cells and basophils. Nature 365: 340–343PubMedGoogle Scholar
  50. 50.
    John ALS, Rathore APS, Yap H et al (2011) Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance. Proc Natl Acad Sci U S A 108: 9190–9195Google Scholar
  51. 51.
    Brown MG, McAlpine SM, Huang YY et al (2012) RNA sensors enable human mast cell anti-viral chemokine production and IFN-mediated protection in response to antibody-enhanced dengue virus infection. PLoS One 7:e34055PubMedCentralPubMedGoogle Scholar
  52. 52.
    Dietrich N, Rohde M, Geffers R et al (2010) Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria. Proc Natl Acad Sci U S A 107: 8748–8753PubMedCentralPubMedGoogle Scholar
  53. 53.
    John ALS, Abraham SN (2013) Innate immunity and its regulation by mast cells. J Immunol 190:4458–4463Google Scholar
  54. 54.
    Sundstrom JB, Ellis JE, Hair GA et al (2007) Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood 109: 5293–5300PubMedGoogle Scholar
  55. 55.
    Kasturiratne A, Wickremasinghe AR, de Silva N et al (2008) The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 5:e218PubMedCentralPubMedGoogle Scholar
  56. 56.
    Biló BM, Rueff F, Mosbech H et al (2005) Diagnosis of Hymenoptera venom allergy. Allergy 60:1339–1349PubMedGoogle Scholar
  57. 57.
    Rueff F, Dugas-Breit S, Przybilla B (2009) Stinging Hymenoptera and mastocytosis. Curr Opin Allergy Clin Immunol 9:338–342PubMedGoogle Scholar
  58. 58.
    Bonadonna P, Zanotti R, Müller U (2010) Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol 10:347–353PubMedGoogle Scholar
  59. 59.
    Casewell NR, Wüster W, Vonk FJ et al (2013) Complex cocktails: the evolutionary novelty of venoms. Trends Ecol Evol 28:219–229PubMedGoogle Scholar
  60. 60.
    Brown TC, Tankersley MS (2011) The sting of the honeybee: an allergic perspective. Ann Allergy Asthma Immunol 107:463–470PubMedGoogle Scholar
  61. 61.
    Metz M, Piliponsky AM, Chen C-C et al (2006) Mast cells can enhance resistance to snake and honeybee venoms. Science 313: 526–530PubMedGoogle Scholar
  62. 62.
    Akahoshi M, Song CH, Piliponsky AM et al (2011) Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. J Clin Invest 121:4180–4191PubMedCentralPubMedGoogle Scholar
  63. 63.
    Maurer M, Wedemeyer J, Metz M et al (2004) Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature 432: 512–516PubMedGoogle Scholar
  64. 64.
    Caughey GH (2011) Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol 716:212–234PubMedCentralPubMedGoogle Scholar
  65. 65.
    Siddiqui S, Mistry V, Doe C et al (2008) Airway hyperresponsiveness is dissociated from airway wall structural remodeling. J Allergy Clin Immunol 122:335.e3–341.e3Google Scholar
  66. 66.
    Carroll NG, Mutavdzic S, James AL (2002) Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 19:879–885PubMedGoogle Scholar
  67. 67.
    Leckie MJ, ten Brinke A, Khan J et al (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsìveness, and the late asthmatic response. Lancet 356:2144–2148PubMedGoogle Scholar
  68. 68.
    Nair P, Pizzichini MMM, Kjarsgaard M et al (2009) Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 360:985–993PubMedGoogle Scholar
  69. 69.
    Crimi E, Chiaramondia M, Milanese M et al (1991) Increased numbers of mast cells in bronchial mucosa after the late-phase asthmatic response to allergen. Am Rev Respir Dis 144:1282–1286PubMedGoogle Scholar
  70. 70.
    Busse W, Corren J, Lanier BQ et al (2001) Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 108:184–190PubMedGoogle Scholar
  71. 71.
    Holgate ST, Djukanović R, Casale T et al (2005) Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy. Clin Exp Allergy 35:408–416PubMedGoogle Scholar
  72. 72.
    Krishna MT, Chauhan A, Little L et al (2001) Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma. J Allergy Clin Immunol 107:1039–1045PubMedGoogle Scholar
  73. 73.
    Bischoff SC (2007) Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7:93–104PubMedGoogle Scholar
  74. 74.
    Rock JR, Randell SH, Hogan BLM (2010) Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis Model Mech 3:545–556PubMedCentralPubMedGoogle Scholar
  75. 75.
    Becker M, Reuter S, Friedrich P et al (2011) Genetic variation determines mast cell functions in experimental asthma. J Immunol 186: 7225–7231PubMedGoogle Scholar
  76. 76.
    Grimbaldeston MA, Chen C-C, Piliponsky AM et al (2005) Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 167:835–848PubMedCentralPubMedGoogle Scholar
  77. 77.
    Nakae S, Ho LH, Yu M et al (2007) Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice. J Allergy Clin Immunol 120:48–55PubMedGoogle Scholar
  78. 78.
    Rodewald H-R, Feyerabend TB (2012) Widespread immunological functions of mast cells: fact or fiction? Immunity 37:13–24PubMedGoogle Scholar
  79. 79.
    Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640PubMedGoogle Scholar
  80. 80.
    Baumgart DC, Sandborn WJ (2007) Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369:1641–1657PubMedGoogle Scholar
  81. 81.
    Farhadi A, Fields J-Z, Keshavarzian A (2007) Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: stress, intestinal hyperpermeability and inflammation. World J Gastroenterol 13: 3027–3030PubMedCentralPubMedGoogle Scholar
  82. 82.
    Matricon J, Meleine M, Gelot A et al (2012) Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 36:1009–1031PubMedGoogle Scholar
  83. 83.
    Nolte H, Spjeldnaes N, Kruse A et al (1990) Histamine release from gut mast cells from patients with inflammatory bowel diseases. Gut 31:791–794PubMedCentralPubMedGoogle Scholar
  84. 84.
    Lilja I, Gustafson-Svärd C, Franzén L et al (2000) Tumor necrosis factor-alpha in ileal mast cells in patients with Crohn’s disease. Digestion 61:68–76PubMedGoogle Scholar
  85. 85.
    Stoyanova II, Gulubova MV (2002) Mast cells and inflammatory mediators in chronic ulcerative colitis. Acta Histochem 104:185–192PubMedGoogle Scholar
  86. 86.
    Hodges K, Kennedy L, Meng F et al (2012) Mast cells, disease and gastrointestinal cancer: a comprehensive review of recent findings. Transl Gastrointest Cancer 1:138–150PubMedCentralPubMedGoogle Scholar
  87. 87.
    Odenwald MA, Turner JR (2013) Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol 11(9):1075–1083PubMedCentralPubMedGoogle Scholar
  88. 88.
    Stead RH, Dixon MF, Bramwell NH et al (1989) Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. Gastroenterology 97:575–585PubMedGoogle Scholar
  89. 89.
    Wood JD (2004) Enteric neuroimmunophysiology and pathophysiology. Gastroenterology 127:635–657PubMedGoogle Scholar
  90. 90.
    Kurashima Y, Amiya T, Nochi T et al (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 3:1034PubMedCentralPubMedGoogle Scholar
  91. 91.
    Konturek PC, Brzozowski T, Konturek SJ (2011) Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol 62: 591–599PubMedGoogle Scholar
  92. 92.
    Farhadi A, Keshavarzian A, Van de Kar LD et al (2005) Heightened responses to stressors in patients with inflammatory bowel disease. Am J Gastroenterol 100:1796–1804PubMedGoogle Scholar
  93. 93.
    Valatas V, Vakas M, Kolios G (2013) The value of experimental models of colitis in predicting efficacy of biologic therapies for inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol 305:G763–G785PubMedGoogle Scholar
  94. 94.
    Middel P, Reich K, Polzien F et al (2001) Interleukin 16 expression and phenotype of interleukin 16 producing cells in Crohn’s disease. Gut 49:795–803PubMedCentralPubMedGoogle Scholar
  95. 95.
    Barrett KE, Tashof TL, Metcalfe DD (1985) Inhibition of IgE-mediated mast cell degranulation by sulphasalazine. Eur J Pharmacol 107:279–281PubMedGoogle Scholar
  96. 96.
    De Winter BY, van den Wijngaard RM, de Jonge WJ (2012) Intestinal mast cells in gut inflammation and motility disturbances. Biochim Biophys Acta 1822:66–73PubMedGoogle Scholar
  97. 97.
    Barbara G, Stanghellini V, De Giorgio R et al (2006) Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 18:6–17PubMedGoogle Scholar
  98. 98.
    Stefanini GF, Prati E, Albini MC et al (1992) Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type. Am J Gastroenterol 87:55–57PubMedGoogle Scholar
  99. 99.
    Matter SE, Bhatia PS, Miner PB Jr (1990) Evaluation of antral mast cells in nonulcer dyspepsia. Dig Dis Sci 35:1358–1363PubMedGoogle Scholar
  100. 100.
    Clouse RE, Lustman PJ, Geisman RA et al (1994) Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience. Aliment Pharmacol Ther 8:409–416PubMedGoogle Scholar
  101. 101.
    Kaartinen M, Penttilä A, Kovanen PT (1994) Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 90:1669–1678PubMedGoogle Scholar
  102. 102.
    Tsunemi K, Takai S, Nishimoto M et al (2002) Possible roles of angiotensin II-forming enzymes, angiotensin converting enzyme and chymase-like enzyme, in the human aneurysmal aorta. Hypertens Res 25:817–822PubMedGoogle Scholar
  103. 103.
    Kovanen PT (2007) Mast cells: multipotent local effector cells in atherothrombosis. Immunol Rev 217:105–122PubMedGoogle Scholar
  104. 104.
    Lindstedt KA, Mäyränpää MI, Kovanen PT (2007) Mast cells in vulnerable atherosclerotic plaques—a view to a kill. J Cell Mol Med 11:739–758PubMedGoogle Scholar
  105. 105.
    Bot I, Biessen EAL (2011) Mast cells in atherosclerosis. Thromb Haemost 106: 820–826PubMedGoogle Scholar
  106. 106.
    Xu J-M, Shi G-P (2012) Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases. Endocr Rev 33:71–108PubMedCentralPubMedGoogle Scholar
  107. 107.
    Swedenborg J, Mäyränpää MI, Kovanen PT (2011) Mast cells important players in the orchestrated pathogenesis of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 31:734–740PubMedGoogle Scholar
  108. 108.
    Levick SP, Meléndez GC, Plante E et al (2011) Cardiac mast cells: the centrepiece in adverse myocardial remodelling. Cardiovasc Res 89:12–19PubMedCentralPubMedGoogle Scholar
  109. 109.
    Bot I, van Berkel TJ, Biessen EA (2008) Mast cells: pivotal players in cardiovascular diseases. Curr Cardiol Rev 4:170–178PubMedCentralPubMedGoogle Scholar
  110. 110.
    Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 27:165–197PubMedCentralPubMedGoogle Scholar
  111. 111.
    Cairns A, Constantinides P (1954) Mast cells in human atherosclerosis. Science 120:31–32PubMedGoogle Scholar
  112. 112.
    Jeziorska M, McCollum C, Woolley DE (1997) Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries. J Pathol 182:115–122PubMedGoogle Scholar
  113. 113.
    Kovanen PT (1996) Mast cells in human fatty streaks and atheromas: implications for intimal lipid accumulation. Curr Opin Lipidol 7:281–286PubMedGoogle Scholar
  114. 114.
    Kaartinen M, Penttilä A, Kovanen PT (1996) Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage. Atherosclerosis 123:123–131PubMedGoogle Scholar
  115. 115.
    Willems S, Vink A, Bot I et al (2013) Mast cells in human carotid atherosclerotic plaques are associated with intraplaque microvessel density and the occurrence of future cardiovascular events. Eur Heart J 34(48): 3699–3706PubMedGoogle Scholar
  116. 116.
    Lappalainen H, Laine P, Pentikäinen MO et al (2004) Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator. Arterioscler Thromb Vasc Biol 24:1880–1885PubMedGoogle Scholar
  117. 117.
    Mäyränpää MI, Trosien JA, Fontaine V et al (2009) Mast cells associate with neovessels in the media and adventitia of abdominal aortic aneurysms. J Vasc Surg 50:388–395PubMedGoogle Scholar
  118. 118.
    Tsuruda T, Kato J, Hatakeyama K et al (2008) Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm. Circ Res 102:1368–1377PubMedGoogle Scholar
  119. 119.
    Anvari MS, Boroumand MA, Mojarad EA et al (2012) Do adventitial mast cells contribute to the pathogenesis of ascending thoracic aorta aneurysm? Int J Surg Pathol 20:474–479PubMedGoogle Scholar
  120. 120.
    Pejler G, Ronnberg E, Waern I et al (2010) Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115:4981–4990PubMedGoogle Scholar
  121. 121.
    Furubayashi K, Takai S, Jin D et al (2008) Chymase activates promatrix metalloproteinase-9 in human abdominal aortic aneurysm. Clin Chim Acta 388:214–216PubMedGoogle Scholar
  122. 122.
    Shi G-P, Sukhova GK, Grubb A et al (1999) Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest 104: 1191–1197PubMedCentralPubMedGoogle Scholar
  123. 123.
    Lv B-J, Lindholt JS, Wang J et al (2013) Plasma levels of cathepsins L, K, and V and risks of abdominal aortic aneurysms: a randomized population-based study. Atherosclerosis 230:100–105PubMedCentralPubMedGoogle Scholar
  124. 124.
    Choke E, Thompson MM, Dawson J et al (2006) Abdominal aortic aneurysm rupture is associated with increased medial neovascularization and overexpression of proangiogenic cytokines. Arterioscler Thromb Vasc Biol 26:2077–2082PubMedGoogle Scholar
  125. 125.
    Mayraanpaa MI, Heikkila HM, Lindstedt KA et al (2006) Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion. Coron Artery Dis 17:611–621Google Scholar
  126. 126.
    Patella V, de Crescenzo G, Lamparter-Schummert B et al (1997) Increased cardiac mast cell density and mediator release in patients with dilated cardiomyopathy. Inflamm Res 46:31–32Google Scholar
  127. 127.
    Patella V, Marinò I, Arbustini E et al (1998) Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy. Circulation 97:971–978PubMedGoogle Scholar
  128. 128.
    Ibrahim M, Terracciano C, Yacoub MH (2012) Can bridge to recovery help to reveal the secrets of the failing heart? Curr Cardiol Rep 14:392–396PubMedGoogle Scholar
  129. 129.
    Akgul A, Skrabal CA, Thompson LO et al (2004) Role of mast cells and their mediators in failing myocardium under mechanical ventricular support. J Heart Lung Transplant 23:709–715PubMedGoogle Scholar
  130. 130.
    Jahanyar J, Youker KA, Torre-Amione G et al (2008) Increased expression of stem cell factor and its receptor after left ventricular assist device support: a potential novel target for therapeutic interventions in heart failure. J Heart Lung Transplant 27:701–709PubMedGoogle Scholar
  131. 131.
    Jahanyar J, Youker KA, Loebe M et al (2007) Mast cell-derived cathepsin G: a possible role in the adverse remodeling of the failing human heart. J Surg Res 140:199–203PubMedGoogle Scholar
  132. 132.
    Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737PubMedCentralPubMedGoogle Scholar
  133. 133.
    Qin Y, Shi G-P (2011) Cysteinyl cathepsins and mast cell proteases in the pathogenesis and therapeutics of cardiovascular diseases. Pharmacol Ther 131:338–350PubMedCentralPubMedGoogle Scholar
  134. 134.
    Krauth MT, Majlesi Y, Sonneck K et al (2006) Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells. Allergy 61:281–288PubMedGoogle Scholar
  135. 135.
    Clejan S, Japa S, Clemetson C et al (2002) Blood histamine is associated with coronary artery disease, cardiac events and severity of inflammation and atherosclerosis. J Cell Mol Med 6:583–592PubMedGoogle Scholar
  136. 136.
    Kim J, Ogai A, Nakatani S et al (2006) Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies. J Am Coll Cardiol 48:1378–1384PubMedGoogle Scholar
  137. 137.
    Korkmaz ME, Oto A, Saraclar Y et al (1991) Levels of IgE in the serum of patients with coronary arterial disease. Int J Cardiol 31: 199–204PubMedGoogle Scholar
  138. 138.
    Upadhya B, Kontos JL, Ardeshirpour F et al (2004) Relation of serum levels of mast cell tryptase of left ventricular systolic function, left ventricular volume or congestive heart failure. J Card Fail 10:31–35PubMedGoogle Scholar
  139. 139.
    Deliargyris EN, Upadhya B, Sane DC et al (2005) Mast cell tryptase: a new biomarker in patients with stable coronary artery disease. Atherosclerosis 178:381–386PubMedGoogle Scholar
  140. 140.
    Xiang M, Sun J, Lin Y et al (2011) Usefulness of serum tryptase level as an independent biomarker for coronary plaque instability in a Chinese population. Atherosclerosis 215: 494–499PubMedCentralPubMedGoogle Scholar
  141. 141.
    Duda D, Lorenz W, Celik I (2002) Histamine release in mesenteric traction syndrome during abdominal aortic aneurysm surgery: prophylaxis with H1 and H2 antihistamines. Inflamm Res 51:495–499PubMedGoogle Scholar
  142. 142.
    Longley BJ, Tyrrell L, Lu S-Z et al (1996) Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. Nat Genet 12:312–314PubMedGoogle Scholar
  143. 143.
    Valent P, Horny H-P, Escribano L et al (2001) Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 25:603–625PubMedGoogle Scholar
  144. 144.
    Nagata H, Worobec AS, Oh CK et al (1995) 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 92:10560–10564PubMedCentralPubMedGoogle Scholar
  145. 145.
    Irani AA, Garriga MM, Metcalfe DD et al (1990) Mast cells in cutaneous mastocytosis: accumulation of the MCTC type. Clin Exp Allergy 20:53–58PubMedGoogle Scholar
  146. 146.
    Schwartz LB (2006) Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am 26: 451–463PubMedGoogle Scholar
  147. 147.
    Compton SJ, Cairns JA, Holgate ST et al (2000) Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC). Clin Exp Immunol 121:31–36PubMedCentralPubMedGoogle Scholar
  148. 148.
    He S, Gaça MDA, Walls AF (1998) A role for tryptase in the activation of human mast cells: modulation of histamine release by tryptase and inhibitors of tryptase. J Pharmacol Exp Ther 286:289–297PubMedGoogle Scholar
  149. 149.
    Pardanani A (2013) Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management. Am J Hematol 88: 612–624PubMedGoogle Scholar
  150. 150.
    Pardanani A (2013) How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). Blood 121:3085–3094PubMedGoogle Scholar
  151. 151.
    Horan RF, Sheffer AL, Austen KF (1990) Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 85:852–855PubMedGoogle Scholar
  152. 152.
    Edwards AM, Capková S (2011) Oral and topical sodium cromoglicate in the treatment of diffuse cutaneous mastocytosis in an infant. BMJ Case Rep: bcr0220113910Google Scholar
  153. 153.
    Siebenhaar F, Förtsch A, Krause K et al (2013) Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo-controlled trial. Allergy 68(7):949–952PubMedGoogle Scholar
  154. 154.
    Paraskevopoulos G, Sifnaios E, Christodoulopoulos K et al (2013) Successful treatment of mastocytic anaphylactic episodes with reduction of skin mast cells after anti-IgE therapy. Eur Ann Allergy Clin Immunol 45:52–55PubMedGoogle Scholar
  155. 155.
    Gleixner KV, Mayerhofer M, Aichberger KJ et al (2006) PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects. Blood 107:752–759PubMedGoogle Scholar
  156. 156.
    Gleixner KV, Mayerhofer M, Cerny-Reiterer S et al (2011) KIT-D816V-independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib. Blood 118:1885–1898PubMedGoogle Scholar
  157. 157.
    Agarwala MK, George R, Mathews V et al (2013) Role of imatinib in the treatment of pediatric onset indolent systemic mastocytosis: a case report. J Dermatolog Treat 24: 481–483PubMedGoogle Scholar
  158. 158.
    Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21:309–322PubMedGoogle Scholar
  159. 159.
    Westphal E, Ehrlich P (1891) Über Mastzellen. Histologie und Klinik des Plutes: gesammelte Mitt (h) eilungen, Ehrlich P.. Farbenanalytische Untersuchungen. Hirschwald Press, Berlin, pp 17–21Google Scholar
  160. 160.
    Theoharides TC, Conti P (2004) Mast cells: the JEKYLL and HYDE of tumor growth. Trends Immunol 25:235–241PubMedGoogle Scholar
  161. 161.
    Zhang W, Stoica G, Tasca SI et al (2000) Modulation of tumor angiogenesis by stem cell factor. Cancer Res 60:6757–6762PubMedGoogle Scholar
  162. 162.
    Conti P, Castellani ML, Kempuraj D et al (2007) Role of mast cells in tumor growth. Ann Clin Lab Sci 37:315–322PubMedGoogle Scholar
  163. 163.
    Maltby S, Khazaie K, McNagny KM (2009) Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta 1796(1):19–26PubMedCentralPubMedGoogle Scholar
  164. 164.
    Aaltomaa S, Lipponen P, Papinaho S et al (1993) Mast cells in breast cancer. Anticancer Res 13:785–788PubMedGoogle Scholar
  165. 165.
    Dabiri S, Huntsman D, Makretsov N et al (2004) The presence of stromal mast cells identifies a subset of invasive breast cancers with a favorable prognosis. Mod Pathol 17: 690–695PubMedGoogle Scholar
  166. 166.
    Ribatti D, Finato N, Crivellato E et al (2007) Angiogenesis and mast cells in human breast cancer sentinel lymph nodes with and without micrometastases. Histopathology 51:837–842PubMedGoogle Scholar
  167. 167.
    Ranieri G (2009) Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients. Int J Oncol 35:115–120PubMedGoogle Scholar
  168. 168.
    Rajput AB, Turbin DA, Cheang MC et al (2008) Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat 107:249–257PubMedCentralPubMedGoogle Scholar
  169. 169.
    Amini R-M, Aaltonen K, Nevanlinna H et al (2007) Mast cells and eosinophils in invasive breast carcinoma. BMC Cancer 7:165PubMedCentralPubMedGoogle Scholar
  170. 170.
    Mangia A, Malfettone A, Rossi R et al (2011) Tissue remodelling in breast cancer: human mast cell tryptase as an initiator of myofibroblast differentiation. Histopathology 58: 1096–1106PubMedGoogle Scholar
  171. 171.
    Strouch MJ, Cheon EC, Salabat MR et al (2010) Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res 16: 2257–2265PubMedCentralPubMedGoogle Scholar
  172. 172.
    Cai S-W, Yang S-Z, Gao J et al (2011) Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma. Surgery 149:576–584PubMedGoogle Scholar
  173. 173.
    Chang DZ, Ma Y, Ji B et al (2011) Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. Clin Cancer Res 17:7015–7023PubMedCentralPubMedGoogle Scholar
  174. 174.
    Esposito I, Menicagli M, Funel N et al (2004) Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol 57: 630–636PubMedCentralPubMedGoogle Scholar
  175. 175.
    Nonomura N, Takayama H, Nishimura K et al (2007) Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. Br J Cancer 97:952–956PubMedCentralPubMedGoogle Scholar
  176. 176.
    Fleischmann A, Schlomm T, Köllermann J et al (2009) Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate 69:976–981PubMedGoogle Scholar
  177. 177.
    Pittoni P, Tripodo C, Piconese S et al (2011) Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res 71:5987–5997PubMedGoogle Scholar
  178. 178.
    Pittoni P, Colombo MP (2012) The dark side of mast cell-targeted therapy in prostate cancer. Cancer Res 72:831–835PubMedGoogle Scholar
  179. 179.
    Frenzel L, Hermine O (2013) Mast cells and inflammation. Joint Bone Spine 80:141–145PubMedGoogle Scholar
  180. 180.
    Walker ME, Hatfield JK, Brown MA (2012) New insights into the role of mast cells in autoimmunity: evidence for a common mechanism of action? Biochim Biophys Acta 1822:57–65PubMedGoogle Scholar
  181. 181.
    de Vries VC, Noelle RJ (2010) Mast cell mediators in tolerance. Curr Opin Immunol 22:643–648PubMedGoogle Scholar
  182. 182.
    Neumann J (1890) Ueber das Vorkommen der sogenannten “Mastzellen” bei pathologischen Veränderungen des Gehirns. Virchows Arch Pathol Anat Physiol Klin Med 122:378–380Google Scholar
  183. 183.
    (1963) XVI. Mast cell under pathologic conditions. Ann N Y Acad Sci 103:344–354Google Scholar
  184. 184.
    Ibrahim MZM, Reder AT, Lawand R et al (1996) The mast cells of the multiple sclerosis brain. J Neuroimmunol 70:131–138PubMedGoogle Scholar
  185. 185.
    Krüger PG (2001) Mast cells and multiple sclerosis: a quantitative analysis. Neuropathol Appl Neurobiol 27:275–280PubMedGoogle Scholar
  186. 186.
    Zappulla JP, Arock M, Mars LT et al (2002) Mast cells: new targets for multiple sclerosis therapy? J Neuroimmunol 131:5–20PubMedGoogle Scholar
  187. 187.
    Couturier N, Zappulla JP, Lauwers-Cances V et al (2008) Mast cell transcripts are increased within and outside multiple sclerosis lesions. J Neuroimmunol 195:176–185PubMedGoogle Scholar
  188. 188.
    Karagkouni A, Alevizos M, Theoharides TC (2013) Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev 12: 947–953PubMedGoogle Scholar
  189. 189.
    Brown MA, Hatfield JK (2012) Mast cells are important modifiers of autoimmune disease: with so much evidence, why is there controversy? Front Immunol 3:147PubMedCentralPubMedGoogle Scholar
  190. 190.
    Brown MA, Hatfield JK, Walker ME et al (2012) A game of kit and mouse: the kit is still in the bag. Immunity 36:891–892PubMedGoogle Scholar
  191. 191.
    Feyerabend TB, Weiser A, Tietz A et al (2011) Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 35: 832–844PubMedGoogle Scholar
  192. 192.
    Rodewald H-R (2012) Response to Brown et al. Immunity 36:893–894Google Scholar
  193. 193.
    Sayed BA, Walker ME, Brown MA (2011) Cutting edge: mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J Immunol 186:3294–3298PubMedGoogle Scholar
  194. 194.
    Secor VH, Secor WE, Gutekunst C-A et al (2000) Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J Exp Med 191:813–822PubMedCentralPubMedGoogle Scholar
  195. 195.
    Bennett JL, Blanchet M-R, Zhao L et al (2009) Bone marrow-derived mast cells accumulate in the central nervous system during inflammation but are dispensable for experimental autoimmune encephalomyelitis pathogenesis. J Immunol 182:5507–5514PubMedGoogle Scholar
  196. 196.
    Michel A, Schuler A, Friedrich P et al (2013) Mast cell-deficient KitW-sh “Sash” mutant mice display aberrant myelopoiesis leading to the accumulation of splenocytes that act as myeloid-derived suppressor cells. J Immunol 190:5534–5544PubMedGoogle Scholar
  197. 197.
    Piconese S, Costanza M, Musio S et al (2011) Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice. Lab Invest 91:627–641PubMedGoogle Scholar
  198. 198.
    Li H, Nourbakhsh B, Safavi F et al (2011) Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression. J Immunol 187:274–282PubMedCentralPubMedGoogle Scholar
  199. 199.
    Nigrovic PA, Lee DM (2007) Synovial mast cells: role in acute and chronic arthritis. Immunol Rev 217:19–37PubMedGoogle Scholar
  200. 200.
    Noordenbos T, Yeremenko N, Gofita I et al (2012) Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum 64:99–109PubMedGoogle Scholar
  201. 201.
    Eklund KK (2007) Mast cells in the pathogenesis of rheumatic diseases and as potential targets for anti-rheumatic therapy. Immunol Rev 217:38–52PubMedGoogle Scholar
  202. 202.
    Kenna TJ, Brown MA (2012) The role of IL-17-secreting mast cells in inflammatory joint disease. Nat Rev Rheumatol 9:375–379PubMedGoogle Scholar
  203. 203.
    Sandler C, Lindstedt KA, Joutsiniemi S et al (2007) Selective activation of mast cells in rheumatoid synovial tissue results in production of TNF-α, IL-1β and IL-1Ra. Inflamm Res 56:230–239PubMedGoogle Scholar
  204. 204.
    Hueber AJ, Asquith DL, Miller AM et al (2010) Cutting edge: mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol 184:3336–3340PubMedGoogle Scholar
  205. 205.
    Lee DM, Friend DS, Gurish MF et al (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297:1689–1692PubMedGoogle Scholar
  206. 206.
    Nigrovic PA, Malbec O, Lu B et al (2010) C5a receptor enables participation of mast cells in immune complex arthritis independently of Fcγ receptor modulation. Arthritis Rheum 62:3322–3333PubMedCentralPubMedGoogle Scholar
  207. 207.
    Nigrovic PA, Binstadt BA, Monach PA et al (2007) Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 104:2325–2330PubMedCentralPubMedGoogle Scholar
  208. 208.
    Zhou JS, Xing W, Friend DS et al (2007) Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritis. J Exp Med 204:2797–2802PubMedCentralPubMedGoogle Scholar
  209. 209.
    Holdsworth SR, Summers SA (2008) Role of mast cells in progressive renal diseases. J Am Soc Nephrol 19:2254–2261PubMedGoogle Scholar
  210. 210.
    Tóth T, Tóth-Jakatics R, Jimi S et al (1999) Mast cells in rapidly progressive glomerulonephritis. J Am Soc Nephrol 10:1498–1505PubMedGoogle Scholar
  211. 211.
    Yamada M, Ueda M, Naruko T et al (2001) Mast cell chymase expression and mast cell phenotypes in human rejected kidneys. Kidney Int 59:1374–1381PubMedGoogle Scholar
  212. 212.
    Company C, Piqueras L, Naim Abu Nabah Y et al (2011) Contributions of ACE and mast cell chymase to endogenous angiotensin II generation and leucocyte recruitment in vivo. Cardiovasc Res 92:48–56PubMedGoogle Scholar
  213. 213.
    Wasse H, Naqvi N, Husain A (2012) Impact of mast cell chymase on renal disease progression. Curr Hypertens Rev 8:15–23PubMedCentralPubMedGoogle Scholar
  214. 214.
    Gan P-Y, Summers SA, Ooi JD et al (2012) Mast cells contribute to peripheral tolerance and attenuate autoimmune vasculitis. J Am Soc Nephrol 23:1955–1966PubMedCentralPubMedGoogle Scholar
  215. 215.
    Scandiuzzi L, Beghdadi W, Daugas E et al (2010) Mouse mast cell protease-4 deteriorates renal function by contributing to inflammation and fibrosis in immune complex-mediated glomerulonephritis. J Immunol 185:624–633PubMedCentralPubMedGoogle Scholar
  216. 216.
    Jahanyar J, Koerner MM, Loebe M et al (2008) The role of mast cells after solid organ transplantation. Transplantation 85:1365–1371PubMedGoogle Scholar
  217. 217.
    Ishida T, Hyodo Y, Ishimura T et al (2005) Mast cell numbers and protease expression patterns in biopsy specimens following renal transplantation from living-related donors predict long-term graft function. Clin Transplant 19:817–824PubMedGoogle Scholar
  218. 218.
    Mengel M, Reeve J, Bunnag S et al (2009) Molecular correlates of scarring in kidney transplants: the emergence of mast cell transcripts. Am J Transplant 9:169–178PubMedGoogle Scholar
  219. 219.
    Kalesnikoff J, Galli SJ (2008) New developments in mast cell biology. Nat Immunol 9:1215–1223PubMedCentralPubMedGoogle Scholar
  220. 220.
    de Vries VC, Pino-Lagos K, Nowak EC et al (2011) Mast cells condition dendritic cells to mediate allograft tolerance. Immunity 35: 550–561PubMedCentralPubMedGoogle Scholar
  221. 221.
    de Vries VC, Wasiuk A, Bennett KA et al (2009) Mast cell degranulation breaks peripheral tolerance. Am J Transplant 9: 2270–2280PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Erin J. DeBruin
    • 1
  • Matthew Gold
    • 1
  • Bernard C. Lo
    • 1
  • Kimberly Snyder
    • 1
  • Alissa Cait
    • 2
  • Nikola Lasic
    • 3
  • Martin Lopez
    • 3
  • Kelly M. McNagny
    • 3
  • Michael R. Hughes
    • 1
    Email author
  1. 1.Department of Experimental Medicine, The Biomedical Research CentreThe University of British ColumbiaVancouverCanada
  2. 2.Department of Microbiology and ImmunologyThe University of British ColumbiaVancouverCanada
  3. 3.Department of Medical Genetics, The Biomedical Research CentreThe University of British ColumbiaVancouverCanada

Personalised recommendations