Histochemistry and Cell Biology

, Volume 149, Issue 5, pp 461–477 | Cite as

Tryptase as a polyfunctional component of mast cells

  • Dmitri Atiakshin
  • Igor Buchwalow
  • Vera Samoilova
  • Markus Tiemann


Mast cells are haematopoietic cells that arise from pluripotent precursors of the bone marrow. They play immunomodulatory roles in both health and disease. When appropriately activated, mast cells undergo degranulation, and preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on various inflammatory settings are closely associated with the enzymatic characteristics of tryptase, the main granule compound of mast cells. Tryptase degranulation is often linked with the development of an immune response, allergy, inflammation, and remodelling of tissue architecture. Tryptase also represents an informative diagnostic marker of certain diseases and a prospective target for pharmacotherapy. In this review, we discuss the current knowledge about mast cell tryptase as one of the mast cell secretome proteases. The main points of the reviewed publications are highlighted with our microscopic images of mast cell tryptases visualized using immunohistochemical staining.


Mast cells Tryptase Secretion Inflammation Immune response Morphogenesis 


Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


  1. Alter SC, Metcalfe DD, Bradford TR, Schwartz LB (1987) Regulation of human mast cell tryptase. Effects of enzyme concentration, ionic strength and the structure and negative charge density of polysaccharides. Biochem J 248:821–827PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alter SC, Kramps JA, Janoff A, Schwartz LB (1990) Interactions of human mast cell tryptase with biological protease inhibitors. Arch Biochem Biophys 276:26–31PubMedCrossRefGoogle Scholar
  3. Ammendola M, Zuccala V, Patruno R, Russo E, Luposella M, Amorosi A, Vescio G, Sammarco G, Montemurro S, De Sarro G, Sacco R, Ranieri G (2013) Tryptase-positive mast cells and angiogenesis in keloids: a new possible post-surgical target for prevention. Updates Surg 65:53–57PubMedCrossRefGoogle Scholar
  4. Ammendola M, Leporini C, Marech I, Gadaleta CD, Scognamillo G, Sacco R, Sammarco G, De Sarro G, Russo E, Ranieri G (2014a) Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy. Biomed Res Int 2014:154702PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ammendola M, Sacco R, Sammarco G, Donato G, Montemurro S, Ruggieri E, Patruno R, Marech I, Cariello M, Vacca A, Gadaleta CD, Ranieri G (2014b) Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance. PLoS One 9:e99512PubMedPubMedCentralCrossRefGoogle Scholar
  6. Ammendola M, Sacco R, Sammarco G, Donato G, Zuccala V, Luposella M, Patruno R, Marech I, Montemurro S, Zizzo N, Gadaleta CD, Ranieri G (2014c) Mast cells density positive to tryptase correlates with angiogenesis in pancreatic ductal adenocarcinoma patients having undergone surgery. Gastroenterol Res Pract 2014:951957PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ammendola M, Patruno R, Sacco R, Marech I, Sammarco G, Zuccala V, Luposella M, Zizzo N, Gadaleta C, Porcelli M, Gadaleta CD, Ribatti D, Ranieri G (2016a) Mast cells positive to tryptase and tumour-associated macrophages correlate with angiogenesis in locally advanced colorectal cancer patients undergone to surgery. Expert Opin Ther Targets 20:533–540PubMedCrossRefGoogle Scholar
  8. Ammendola M, Sacco R, Sammarco G, Piardi T, Zuccala V, Patruno R, Zullo A, Zizzo N, Nardo B, Marech I, Crovace A, Gadaleta CD, Pessaux P, Ranieri G (2016b) Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery. Onco Targets Ther 9:4465–4471PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ammendola M, Sacco R, Zuccala V, Luposella M, Patruno R, Gadaleta P, Zizzo N, Gadaleta CD, De Sarro G, Sammarco G, Oltean M, Ranieri G (2016c) Mast cells density positive to tryptase correlate with microvascular density in both primary gastric cancer tissue and loco-regional lymph node metastases from patients that have undergone radical surgery. Int J Mol Sci 17:1905PubMedCentralCrossRefGoogle Scholar
  10. Annichkov NM, Kostantinov IE (2007) [A. A. Maksimov: on the 100th anniversary of the unitarian theory of hematopoiesis]. Arkh Patol 69:3–7PubMedGoogle Scholar
  11. Atiakshin DA, Bykov EG, Il’in EA, Pashkov AN (2009) [Glycogen content in gerbil’s liver following the spacecraft Foton-M3 mission]. Aviakosm Ekolog Med 43:18–22PubMedGoogle Scholar
  12. Atiakshin DA, Il’in EA, Pashkov AN (2010) [Morphofunctional state of hepatocytes nuclear apparatus in Mongolian herbils after the flight on space apparatus Foton-M3]. Aviakosm Ekolog Med 44:29–34PubMedGoogle Scholar
  13. Atiakshin DA, Bykov EG, Il’in EA, Pashkov AN (2011) [Tissue-specific reaction of the mucous coat of herbals’ small gut under the influence of spaceflight factors on board biosat “Foton M3”]. Aviakosm Ekolog Med 45:25–30PubMedGoogle Scholar
  14. Atiakshin D, Samoilova V, Buchwalow I, Boecker W, Tiemann M (2017) Characterization of mast cell populations using different methods for their identification. Histochem Cell Biol 147:683–694PubMedCrossRefGoogle Scholar
  15. Benitez-Bribiesca L, Wong A, Utrera D, Castellanos E (2001) The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix. J Histochem Cytochem 49:1061–1062PubMedCrossRefGoogle Scholar
  16. Blair RJ, Meng H, Marchese MJ, Ren S, Schwartz LB, Tonnesen MG, Gruber BL (1997) Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Invest 99:2691–2700PubMedPubMedCentralCrossRefGoogle Scholar
  17. Blank U, Madera-Salcedo IK, Danelli L, Claver J, Tiwari N, Sanchez-Miranda E, Vazquez-Victorio G, Ramirez-Valadez KA, Macias-Silva M, Gonzalez-Espinosa C (2014) Vesicular trafficking and signaling for cytokine and chemokine secretion in mast cells. Front Immunol 5:453PubMedPubMedCentralCrossRefGoogle Scholar
  18. Blott EJ, Griffiths GM (2002) Secretory lysosomes. Nat Rev Mol Cell Biol 3:122–131PubMedCrossRefGoogle Scholar
  19. Buchwalow IB, Boecker W (2010) Immunohistochemistry: basics and methods, 1 ed. Heidelberg. Springer, DordrechtCrossRefGoogle Scholar
  20. Buchwalow I, Boecker W, Tiemann M (2015) The contribution of Paul Ehrlich to histochemistry: a tribute on the occasion of the centenary of his death. Virchows Arch 466:111–116PubMedCrossRefGoogle Scholar
  21. Bykov VL (1999) [Secretory mechanisms and secretory products of mast cells]. Morfologiia 115:64–72PubMedGoogle Scholar
  22. Cairns JA (2005) Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders. Pulm Pharmacol Ther 18:55–66PubMedCrossRefGoogle Scholar
  23. Caughey GH (1994) Serine proteinases of mast cell and leukocyte granules. A league of their own. Am J Respir Crit Care Med 150:S138–S142CrossRefGoogle Scholar
  24. Caughey GH (2006) Tryptase genetics and anaphylaxis. J Allergy Clin Immunol 117:1411–1414PubMedPubMedCentralCrossRefGoogle Scholar
  25. Caughey GH (2007) Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev 217:141–154PubMedPubMedCentralCrossRefGoogle Scholar
  26. Caughey GH (2011) Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol 716:212–234PubMedPubMedCentralCrossRefGoogle Scholar
  27. Caughey GH (2016) Mast cell proteases as pharmacological targets. Eur J Pharmacol 778:44–55PubMedCrossRefGoogle Scholar
  28. Corvera CU, Dery O, McConalogue K, Bohm SK, Khitin LM, Caughey GH, Payan DG, Bunnett NW (1997) Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2. J Clin Invest 100:1383–1393PubMedPubMedCentralCrossRefGoogle Scholar
  29. Craig SS, Schwartz LB (1990) Human MCTC type of mast cell granule: the uncommon occurrence of discrete scrolls associated with focal absence of chymase. Lab Invest 63:581–585PubMedGoogle Scholar
  30. Craig SS, Schechter NM, Schwartz LB (1988) Ultrastructural analysis of human T and TC mast cells identified by immunoelectron microscopy. Lab Invest 58:682–691PubMedGoogle Scholar
  31. Crivellato E, Beltrami C, Mallardi F, Ribatti D (2003a) Paul Ehrlich’s doctoral thesis: a milestone in the study of mast cells. Br J Haematol 123:19–21Google Scholar
  32. Crivellato E, Nico B, Vacca A, Ribatti D (2003b) Ultrastructural analysis of mast cell recovery after secretion by piecemeal degranulation in B-cell non-Hodgkin’s lymphoma. Leuk Lymphoma 44:517–521PubMedCrossRefGoogle Scholar
  33. Crivellato E, Nico B, Ribatti D (2008) Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis. Cancer Lett 269:1–6PubMedCrossRefGoogle Scholar
  34. Crivellato E, Travan L, Ribatti D (2015) The phylogenetic profile of mast cells. Methods Mol Biol 1220:11–27PubMedCrossRefGoogle Scholar
  35. Dai H, Korthuis RJ (2011) Mast Cell Proteases and Inflammation. Drug Discov Today Dis Models 8:47–55PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dines KC, Powell HC (1997) Mast cell interactions with the nervous system: relationship to mechanisms of disease. J Neuropathol Exp Neurol 56:627–640PubMedCrossRefGoogle Scholar
  37. Dvorak AM (1989) Human mast cells. Adv Anat Embryol Cell Biol 114:1–107PubMedCrossRefGoogle Scholar
  38. Dvorak AM (1995) Ultrastructural analysis of human mast cells and basophils. Chem Immunol 61:1–33PubMedGoogle Scholar
  39. Dvorak AM (2005a) Degranulation and recovery from degranulation of basophils and mast cells. Chem Immunol Allergy 85:205–251PubMedCrossRefGoogle Scholar
  40. Dvorak AM (2005b) Ultrastructural studies of human basophils and mast cells. J Histochem Cytochem 53:1043–1070PubMedCrossRefGoogle Scholar
  41. Ehrlich P (1878) Beiträge für Theorie und Praxis der histologischen Färbung. Leipzig University, Leipzig, p 65Google Scholar
  42. Estevez MD, Vieytes MR, Louzao MC, Alfonso A, Vilarino N, Botana LM (1997) The antineoplastic drug vinorelbine activates non-immunological histamine release from rat mast cells. Inflamm Res 46:119–124PubMedCrossRefGoogle Scholar
  43. Gaber MA, Seliet IA, Ehsan NA, Megahed MA (2014) Mast cells and angiogenesis in wound healing. Anal Quant Cytopathol Histpathol 36:32–40PubMedGoogle Scholar
  44. Galli SJ, Tsai M (2008) Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis. J Dermatol Sci 49:7–19PubMedCrossRefGoogle Scholar
  45. Galli SJ, Grimbaldeston M, Tsai M (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 8:478–486PubMedPubMedCentralCrossRefGoogle Scholar
  46. Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G (2015) Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol 126:45–127PubMedPubMedCentralCrossRefGoogle Scholar
  47. Galli SJ, Starkl P, Marichal T, Tsai M (2016) Mast cells and IgE in defense against venoms: Possible “good side” of allergy? Allergol Int 65:3–15PubMedCrossRefGoogle Scholar
  48. Glenner GG, Cohen LA (1960) Histochemical demonstration of a species-specific trypsin-like enzyme in mast cells. Nature 185:846–847PubMedCrossRefGoogle Scholar
  49. Goffredo V, Gadaleta CD, Laterza A, Vacca A, Ranieri G (2013) Tryptase serum levels in patients suffering from hepatocellular carcinoma undergoing intra-arterial chemoembolization: possible predictive role of response to treatment. Mol Clin Oncol 1:385–389PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gomori G (1953a) Chloroacyl esters as histochemical substrates. J Histochem Cytochem 1:469–470PubMedCrossRefGoogle Scholar
  51. Gomori G (1953b) Human esterases. J Lab Clin Med 42:445–453PubMedGoogle Scholar
  52. Gruber BL, Kew RR, Jelaska A, Marchese MJ, Garlick J, Ren S, Schwartz LB, Korn JH (1997) Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 158:2310–2317PubMedGoogle Scholar
  53. Hallgren J, Gurish MF (2014) Granule maturation in mast cells: histamine in control. Eur J Immunol 44:33–36PubMedCrossRefGoogle Scholar
  54. Hallgren J, Pejler G (2006) Biology of mast cell tryptase. An inflammatory mediator. FEBS J 273:1871–1895PubMedCrossRefGoogle Scholar
  55. Hallgren J, Spillmann D, Pejler G (2001) Structural requirements and mechanism for heparin-induced activation of a recombinant mouse mast cell tryptase, mouse mast cell protease-6: formation of active tryptase monomers in the presence of low molecular weight heparin. J Biol Chem 276:42774–42781PubMedCrossRefGoogle Scholar
  56. Hernández-Hernández L, Sanz C, García-Solaesa V, Padrón J, García-Sánchez A, Dávila I, Isidoro-García M, Lorente F (2012) Tryptase: genetic and functional considerations. Allergol Immunopathol 40:385–389CrossRefGoogle Scholar
  57. Huang C, De Sanctis GT, O’Brien PJ, Mizgerd JP, Friend DS, Drazen JM, Brass LF, Stevens RL (2001) Evaluation of the substrate specificity of human mast cell tryptase beta I and demonstration of its importance in bacterial infections of the lung. J Biol Chem 276:26276–26284PubMedCrossRefGoogle Scholar
  58. Huntington JA, Read RJ, Carrell RW (2000) Structure of a serpin-protease complex shows inhibition by deformation. Nature 407:923–926PubMedCrossRefGoogle Scholar
  59. Imada A, Shijubo N, Kojima H, Abe S (2000) Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur Respir J 15:1087–1093PubMedCrossRefGoogle Scholar
  60. Johnson JL, Jackson CL, Angelini GD, George SJ (1998) Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 18:1707–1715PubMedCrossRefGoogle Scholar
  61. Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T (2011) Nonredundant roles of basophils in immunity. Annu Rev Immunol 29:45–69PubMedCrossRefGoogle Scholar
  62. Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y (2017) Multifaceted roles of basophils in health and disease. J Allergy Clin Immunol 140:1473–1476CrossRefGoogle Scholar
  63. Konstantinov IE (2000) In search of Alexander A. Maximow: the man behind the unitarian theory of hematopoiesis. Perspect Biol Med 43:269–276PubMedCrossRefGoogle Scholar
  64. Kovacs P, Hernadi I, Wilhelm M (2006) Mast cells modulate maintained neuronal activity in the thalamus in vivo. J Neuroimmunol 171:1–7PubMedCrossRefGoogle Scholar
  65. Krishnaswamy G, Kelley J, Johnson D, Youngberg G, Stone W, Huang SK, Bieber J, Chi DS (2001) The human mast cell: functions in physiology and disease. Front Biosci 6:D1109–D1127CrossRefGoogle Scholar
  66. Krishnaswamy G, Ajitawi O, Chi DS (2006) The human mast cell: an overview. Methods Mol Biol 315:13–34PubMedGoogle Scholar
  67. Krystel-Whittemore M, Dileepan KN, Wood JG (2015) Mast cell: a multi-functional master cell. Front Immunol 6:620PubMedGoogle Scholar
  68. Kubo M (2016) Basophil and mast cells—their similarity and functional difference. Arerugi 65:926–931PubMedGoogle Scholar
  69. Lagunoff D (1972) Contributions of electron microscopy to the study of mast cells. J Invest Dermatol 58:296–311PubMedCrossRefGoogle Scholar
  70. Le QT, Min HK, Xia HZ, Fukuoka Y, Katunuma N, Schwartz LB (2011) Promiscuous processing of human alphabeta-protryptases by cathepsins L, B, and C. J Immunol 186:7136–7143PubMedPubMedCentralCrossRefGoogle Scholar
  71. Levi-Schaffer F, Piliponsky AM (2003) Tryptase, a novel link between allergic inflammation and fibrosis. Trends Immunol 24:158–161PubMedCrossRefGoogle Scholar
  72. Lundequist A, Boyce JA (2011) LPA5 is abundantly expressed by human mast cells and important for lysophosphatidic acid induced MIP-1beta release. PLoS One 6:e18192PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lundequist A, Pejler G (2011) Biological implications of preformed mast cell mediators. Cell Mol Life Sci 68:965–975PubMedCrossRefGoogle Scholar
  74. Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O’Connell MP, Trivedi NN, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD (2016) Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet 48:1564–1569PubMedPubMedCentralCrossRefGoogle Scholar
  75. Malfettone A, Silvestris N, Saponaro C, Ranieri G, Russo A, Caruso S, Popescu O, Simone G, Paradiso A, Mangia A (2013) High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression. J Cell Mol Med 17:1025–1037PubMedPubMedCentralCrossRefGoogle Scholar
  76. Marech I, Ammendola M, Sacco R, Capriuolo GS, Patruno R, Rubini R, Luposella M, Zuccala V, Savino E, Gadaleta CD, Ribatti D, Ranieri G (2014) Serum tryptase, mast cells positive to tryptase and microvascular density evaluation in early breast cancer patients: possible translational significance. BMC Cancer 14:534PubMedPubMedCentralCrossRefGoogle Scholar
  77. Maximow A (1909) Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematologica 8:125–134Google Scholar
  78. Metcalfe DD, Baram D, Mekori YA (1997) Mast cells. Physiol Rev 77:1033–1079PubMedCrossRefGoogle Scholar
  79. Molinari JF, Scuri M, Moore WR, Clark J, Tanaka R, Abraham WM (1996) Inhaled tryptase causes bronchoconstriction in sheep via histamine release. Am J Respir Crit Care Med 154:649–653PubMedCrossRefGoogle Scholar
  80. Nico B, Marzullo A, Corsi P, Vacca A, Roncali L, Ribatti D (2004) A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of Duchenne muscular dystrophy. Neuroscience 123:585–588PubMedCrossRefGoogle Scholar
  81. Pejler G, Abrink M, Ringvall M, Wernersson S (2007) Mast cell proteases. Adv Immunol 95:167–255PubMedCrossRefGoogle Scholar
  82. Pejler G, Ronnberg E, Waern I, Wernersson S (2010) Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115:4981–4990PubMedCrossRefGoogle Scholar
  83. Pejler G, Hu Frisk JM, Sjostrom D, Paivandy A, Ohrvik H (2017) Acidic pH is essential for maintaining mast cell secretory granule homeostasis. Cell Death Dis 8:e2785PubMedPubMedCentralCrossRefGoogle Scholar
  84. Ribatti D (2016a) The development of human mast cells. An historical reappraisal. Exp Cell Res 342:210–215PubMedCrossRefGoogle Scholar
  85. Ribatti D (2016b) Mast cells as therapeutic target in cancer. Eur J Pharmacol 778:152–157PubMedCrossRefGoogle Scholar
  86. Ribatti D (2016c) Mast cells in lymphomas. Crit Rev Oncol Hematol 101:207–212PubMedCrossRefGoogle Scholar
  87. Ribatti D, Crivellato E (2012) Mast cells, angiogenesis, and tumour growth. Biochim Biophys Acta 1822:2–8PubMedCrossRefGoogle Scholar
  88. Ribatti D, Crivellato E (2016) The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples. Exp Cell Res 341:105–109PubMedCrossRefGoogle Scholar
  89. Ribatti D, Ranieri G (2015) Tryptase, a novel angiogenic factor stored in mast cell granules. Exp Cell Res 332:157–162PubMedCrossRefGoogle Scholar
  90. Ronnberg E, Pejler G (2012) Serglycin: the master of the mast cell. Methods Mol Biol 836:201–217PubMedCrossRefGoogle Scholar
  91. Ronnberg E, Melo FR, Pejler G (2012) Mast cell proteoglycans. J Histochem Cytochem 60:950–962PubMedPubMedCentralCrossRefGoogle Scholar
  92. Rothe MJ, Nowak M, Kerdel FA (1990) The mast cell in health and disease. J Am Acad Dermatol 23:615–624PubMedCrossRefGoogle Scholar
  93. Schwartz LB (1990) Tryptase, a mediator of human mast cells. J Allergy Clin Immunol 86:594–598PubMedCrossRefGoogle Scholar
  94. Schwartz LB, Atkins PC, Bradford TR, Fleekop P, Shalit M, Zweiman B (1987a) Release of tryptase together with histamine during the immediate cutaneous response to allergen. J Allergy Clin Immunol 80:850–855PubMedCrossRefGoogle Scholar
  95. Schwartz LB, Irani AM, Roller K, Castells MC, Schechter NM (1987b) Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 138:2611–2615PubMedGoogle Scholar
  96. Selwood T, Smolensky H, McCaslin DR, Schechter NM (2005) The interaction of human tryptase-beta with small molecule inhibitors provides new insights into the unusual functional instability and quaternary structure of the protease. Biochemistry 44:3580–3590PubMedCrossRefGoogle Scholar
  97. Shukla SA, Veerappan R, Whittimore JS, Ellen Miller L, Youngberg GA (2006) Mast cell ultrastructure and staining in tissue. Methods Mol Biol 315:63–76PubMedGoogle Scholar
  98. Silverman AJ, Sutherland AK, Wilhelm M, Silver R (2000) Mast cells migrate from blood to brain. J Neurosci 20:401–408PubMedCrossRefGoogle Scholar
  99. Singh J, Shah R, Singh D (2016) Targeting mast cells: uncovering prolific therapeutic role in myriad diseases. Int Immunopharmacol 40:362–384PubMedCrossRefGoogle Scholar
  100. Somasundaram P, Ren G, Nagar H, Kraemer D, Mendoza L, Michael LH, Caughey GH, Entman ML, Frangogiannis NG (2005) Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts. J Pathol 205:102–111PubMedPubMedCentralCrossRefGoogle Scholar
  101. Soto D, Malmsten C, Blount JL, Muilenburg DJ, Caughey GH (2002) Genetic deficiency of human mast cell alpha-tryptase. Clin Exp Allergy 32:1000–1006PubMedCrossRefGoogle Scholar
  102. Steinhoff M, Buddenkotte J, Shpacovitch V, Rattenholl A, Moormann C, Vergnolle N, Luger TA, Hollenberg MD (2005) Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev 26:1–43PubMedCrossRefGoogle Scholar
  103. Syväranta S, Helske S, Laine M, Lappalainen J, Kupari M, Mayranpaa MI, Lindstedt KA, Kovanen PT (2010) Vascular endothelial growth factor-secreting mast cells and myofibroblasts: a novel self-perpetuating angiogenic pathway in aortic valve stenosis. Arterioscler Thromb Vasc Biol 30:1220–1227PubMedCrossRefGoogle Scholar
  104. Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, Asadi S, Vasiadi M, Weng Z, Miniati A, Kalogeromitros D (2012) Mast cells and inflammation. Biochim Biophys Acta 1822:21–33PubMedCrossRefGoogle Scholar
  105. Trivedi NN, Caughey GH (2010) Mast cell peptidases: chameleons of innate immunity and host defense. Am J Respir Cell Mol Biol 42:257–267PubMedCrossRefGoogle Scholar
  106. Trivedi NN, Tong Q, Raman K, Bhagwandin VJ, Caughey GH (2007) Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebrates. J Immunol 179:6072–6079PubMedPubMedCentralCrossRefGoogle Scholar
  107. Tsutsui H, Yamanishi Y, Ohtsuka H, Sato S, Yoshikawa S, Karasuyama H (2017) The basophil-specific protease mMCP-8 provokes an inflammatory response in the skin with microvascular hyperpermeability and leukocyte infiltration. J Biol Chem 292:1061–1067PubMedCrossRefGoogle Scholar
  108. Ui H, Andoh T, Lee JB, Nojima H, Kuraishi Y (2006) Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur J Pharmacol 530:172–178PubMedCrossRefGoogle Scholar
  109. Vitte J (2015) Human mast cell tryptase in biology and medicine. Mol Immunol 63:18–24PubMedCrossRefGoogle Scholar
  110. Vukman KV, Forsonits A, Oszvald A, Toth EA, Buzas EI (2017) Mast cell secretome: soluble and vesicular components. Semin Cell Dev Biol 67:65–73PubMedCrossRefGoogle Scholar
  111. Vyas H, Krishnaswamy G (2006) Paul Ehrlich’s “Mastzellen”—from aniline dyes to DNA chip arrays: a historical review of developments in mast cell research. Methods Mol Biol 315:3–11PubMedGoogle Scholar
  112. Welle MM, Audige L, Belz JP (1997) The equine endometrial mast cell during the puerperal period: evaluation of mast cell numbers and types in comparison to other inflammatory changes. Vet Pathol 34:23–30PubMedCrossRefGoogle Scholar
  113. Wernersson S, Pejler G (2014) Mast cell secretory granules: armed for battle. Nat Rev Immunol 14:478–494PubMedCrossRefGoogle Scholar
  114. Whitaker-Menezes D, Schechter NM, Murphy GF (1995) Serine proteinases are regionally segregated within mast cell granules. Lab Invest 72:34–41PubMedGoogle Scholar
  115. Wilhelm M, Silver R, Silverman AJ (2005) Central nervous system neurons acquire mast cell products via transgranulation. Eur J Neurosci 22:2238–2248PubMedPubMedCentralCrossRefGoogle Scholar
  116. Williams CM, Galli SJ (2000) Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 192:455–462PubMedPubMedCentralCrossRefGoogle Scholar
  117. Wolters PJ, Pham CT, Muilenburg DJ, Ley TJ, Caughey GH (2001) Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J Biol Chem 276:18551–18556PubMedCrossRefGoogle Scholar
  118. Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ (2006) Mast cells can promote the development of multiple features of chronic asthma in mice. J Clin Invest 116:1633–1641PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Dmitri Atiakshin
    • 1
  • Igor Buchwalow
    • 2
  • Vera Samoilova
    • 2
  • Markus Tiemann
    • 2
  1. 1.Research Institute of Experimental Biology and MedicineVoronezh N. N. Burdenko State Medical UniversityVoronezhRussia
  2. 2.Institute for HematopathologyHamburgGermany

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