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Mast cell-derived mediators

Michael Gurish, PhD
Mariana C Castells, MD, PhD
Section Editor
Sarbjit Saini, MD
Deputy Editor
Anna M Feldweg, MD


Mast cells release various mediators upon activation, which are responsible for many of the systems of allergic disease and anaphylaxis. These mediators can be divided into three overlapping categories: preformed mediators, newly synthesized lipid mediators, and cytokines and chemokines.

This topic will review mast cell mediators. The information in this topic pertains to human mast cells whenever possible, and notation is made when data are derived purely from murine studies. The development, physiologic roles, surface receptors, and signal transduction of mast cells are reviewed separately. (See "Mast cells: Development, identification, and physiologic roles" and "Mast cells: Surface receptors and signal transduction".)


Mast cell secretory granules contain preformed mediators that are rapidly (within seconds to minutes) released into the extracellular environment upon cell stimulation. These mediators include histamine, neutral proteases, proteoglycans, and some cytokines, such as tumor necrosis factor-alpha (TNF-alpha). They are responsible for many of the acute signs and symptoms of mast cell-mediated allergic reactions, including edema, bronchoconstriction, and increased vascular permeability. Specific pharmacotherapy to inhibit and/or antagonize mast cell mediators is reviewed elsewhere. (See "Systemic mastocytosis: Management and prognosis", section on 'Pharmacotherapy for symptoms related to mast cell mediators'.)

Histamine — Histamine is produced predominantly by mast cells but also is elaborated by basophils, neutrophils [1], and platelets. It is stored in both scroll-like and lattice secretory granules of the human mast cell [2]. Human cutaneous mast cells are estimated to contain 1.9 micrograms of histamine per 106 cells [3]. Secretory granule exocytosis and release of histamine occurs rapidly after either immunoglobulin E (IgE)- or non-IgE-based stimulation [4]. The effects of histamine are mediated through H1, H2, H3, and H4 receptors located on target cells:

H1-mediated actions include increased venular permeability, bronchial and intestinal smooth muscle contraction, increased nasal mucus production, widened pulse pressure, increased heart rate and cardiac output, flushing, and T cell neutrophil and eosinophil chemotaxis [5,6]. In mice, lack of H1 receptors leads to reduced lung inflammation as a consequence of the decreased T cell influx [6].


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  1. Xu X, Zhang D, Zhang H, et al. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med 2006; 203:2907.
  2. Dvorak AM, Costa JJ, Morgan ES, et al. Diamine oxidase-gold ultrastructural localization of histamine in human skin biopsies containing mast cells stimulated to degranulate in vivo by exposure to recombinant human stem cell factor. Blood 1997; 90:2893.
  3. Schwartz LB, Irani AM, Roller K, et al. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 1987; 138:2611.
  4. Lowman MA, Rees PH, Benyon RC, Church MK. Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli. J Allergy Clin Immunol 1988; 81:590.
  5. Marshall JS, Jawdat DM. Mast cells in innate immunity. J Allergy Clin Immunol 2004; 114:21.
  6. Bryce PJ, Mathias CB, Harrison KL, et al. The H1 histamine receptor regulates allergic lung responses. J Clin Invest 2006; 116:1624.
  7. Leino L, Lilius EM. Histamine receptors on leukocytes are expressed differently in vitro and ex vivo. Int Arch Allergy Appl Immunol 1990; 91:30.
  8. Falus A, Merétey K. Histamine: an early messenger in inflammatory and immune reactions. Immunol Today 1992; 13:154.
  9. Arrang JM, Devaux B, Chodkiewicz JP, Schwartz JC. H3-receptors control histamine release in human brain. J Neurochem 1988; 51:105.
  10. Varty LM, Gustafson E, Laverty M, Hey JA. Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction. Eur J Pharmacol 2004; 484:83.
  11. Morse KL, Behan J, Laz TM, et al. Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther 2001; 296:1058.
  12. Holm J, Hansen SI. Ligand binding characteristics and aggregation behavior of purified cow's milk folate binding protein depends on the presence of amphiphatic substances including cholesterol, phospholipids, and synthetic detergents. Biosci Rep 2002; 22:431.
  13. Dunford PJ, O'Donnell N, Riley JP, et al. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 2006; 176:7062.
  14. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther 2003; 305:1212.
  15. Ling P, Ngo K, Nguyen S, et al. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004; 142:161.
  16. Moskovskiĭ AV. [Human tooth development in antenatal period (a luminescent-histochemical study)]. Morfologiia 2005; 128:45.
  17. Kushnir-Sukhov NM, Brown JM, Wu Y, et al. Human mast cells are capable of serotonin synthesis and release. J Allergy Clin Immunol 2007; 119:498.
  18. Avraham S, Austen KF, Nicodemus CF, et al. Cloning and characterization of the mouse gene that encodes the peptide core of secretory granule proteoglycans and expression of this gene in transfected rat-1 fibroblasts. J Biol Chem 1989; 264:16719.
  19. Stevens RL, Fox CC, Lichtenstein LM, Austen KF. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. Proc Natl Acad Sci U S A 1988; 85:2284.
  20. Pejler G, Rönnberg E, Waern I, Wernersson S. Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 2010; 115:4981.
  21. Schwartz LB, Riedel C, Caulfield JP, et al. Cell association of complexes of chymase, heparin proteoglycan, and protein after degranulation by rat mast cells. J Immunol 1981; 126:2071.
  22. Goldstein SM, Leong J, Schwartz LB, Cooke D. Protease composition of exocytosed human skin mast cell protease-proteoglycan complexes. Tryptase resides in a complex distinct from chymase and carboxypeptidase. J Immunol 1992; 148:2475.
  23. Ghildyal N, Friend DS, Stevens RL, et al. Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood. J Exp Med 1996; 184:1061.
  24. Oscarsson LG, Pejler G, Lindahl U. Location of the antithrombin-binding sequence in the heparin chain. J Biol Chem 1989; 264:296.
  25. Weiler JM, Yurt RW, Fearon DT, Austen KF. Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. J Exp Med 1978; 147:409.
  26. Gospodarowicz D, Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 1986; 128:475.
  27. Murakami M, Nakatani Y, Kudo I. Type II secretory phospholipase A2 associated with cell surfaces via C-terminal heparin-binding lysine residues augments stimulus-initiated delayed prostaglandin generation. J Biol Chem 1996; 271:30041.
  28. Bingham CO 3rd, Murakami M, Fujishima H, et al. A heparin-sensitive phospholipase A2 and prostaglandin endoperoxide synthase-2 are functionally linked in the delayed phase of prostaglandin D2 generation in mouse bone marrow-derived mast cells. J Biol Chem 1996; 271:25936.
  29. Pejler G, Sadler JE. Mechanism by which heparin proteoglycan modulates mast cell chymase activity. Biochemistry 1999; 38:12187.
  30. Thompson HL, Schulman ES, Metcalfe DD. Identification of chondroitin sulfate E in human lung mast cells. J Immunol 1988; 140:2708.
  31. Irani AA, Schechter NM, Craig SS, et al. Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A 1986; 83:4464.
  32. Schwartz LB. Effector cells of anaphylaxis: mast cells and basophils. Novartis Found Symp 2004; 257:65.
  33. Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol 1987; 138:2184.
  34. Schwartz LB, Yunginger JW, Miller J, et al. Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 1989; 83:1551.
  35. Caughey GH. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol 2006; 117:1411.
  36. HOPSU VK, GLENNER GG. A histochemical enzyme kinetic system applied to the trypsin-like amidase and esterase activity in human mast cells. J Cell Biol 1963; 17:503.
  37. Schwartz LB, Lewis RA, Austen KF. Tryptase from human pulmonary mast cells. Purification and characterization. J Biol Chem 1981; 256:11939.
  38. Schwartz LB, Bradford TR, Littman BH, Wintroub BU. The fibrinogenolytic activity of purified tryptase from human lung mast cells. J Immunol 1985; 135:2762.
  39. Prieto-García A, Castells MC, Hansbro PM, Stevens RL. Mast cell-restricted tetramer-forming tryptases and their beneficial roles in hemostasis and blood coagulation. Immunol Allergy Clin North Am 2014; 34:263.
  40. Gruber BL, Marchese MJ, Suzuki K, et al. Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation. J Clin Invest 1989; 84:1657.
  41. Tam EK, Caughey GH. Degradation of airway neuropeptides by human lung tryptase. Am J Respir Cell Mol Biol 1990; 3:27.
  42. Caughey GH. Roles of mast cell tryptase and chymase in airway function. Am J Physiol 1989; 257:L39.
  43. Gruber BL, Kew RR, Jelaska A, et al. Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 1997; 158:2310.
  44. Ruoss SJ, Hartmann T, Caughey GH. Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest 1991; 88:493.
  45. Walls AF, He S, Teran LM, et al. Granulocyte recruitment by human mast cell tryptase. Int Arch Allergy Immunol 1995; 107:372.
  46. Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol 1996; 156:275.
  47. Ui H, Andoh T, Lee JB, et al. 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 2006; 530:172.
  48. Irani AM, Craig SS, DeBlois G, et al. Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. J Immunol 1987; 138:4381.
  49. Dougherty RH, Sidhu SS, Raman K, et al. Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol 2010; 125:1046.
  50. Abonia JP, Blanchard C, Butz BB, et al. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 2010; 126:140.
  51. Weidner N, Austen KF. Heterogeneity of mast cells at multiple body sites. Fluorescent determination of avidin binding and immunofluorescent determination of chymase, tryptase, and carboxypeptidase content. Pathol Res Pract 1993; 189:156.
  52. Irani AM, Goldstein SM, Wintroub BU, et al. Human mast cell carboxypeptidase. Selective localization to MCTC cells. J Immunol 1991; 147:247.
  53. Reynolds DS, Gurley DS, Austen KF. Cloning and characterization of the novel gene for mast cell carboxypeptidase A. J Clin Invest 1992; 89:273.
  54. Goldstein SM, Kaempfer CE, Proud D, et al. Detection and partial characterization of a human mast cell carboxypeptidase. J Immunol 1987; 139:2724.
  55. Goldstein SM, Kaempfer CE, Kealey JT, Wintroub BU. Human mast cell carboxypeptidase. Purification and characterization. J Clin Invest 1989; 83:1630.
  56. Goldstein SM, Leong J, Bunnett NW. Human mast cell proteases hydrolyze neurotensin, kinetensin and Leu5-enkephalin. Peptides 1991; 12:995.
  57. Metz M, Piliponsky AM, Chen CC, et al. Mast cells can enhance resistance to snake and honeybee venoms. Science 2006; 313:526.
  58. Schneider LA, Schlenner SM, Feyerabend TB, et al. Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin. J Exp Med 2007; 204:2629.
  59. Schechter NM, Irani AM, Sprows JL, et al. Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell. J Immunol 1990; 145:2652.
  60. Wintroub BU, Schechter NB, Lazarus GS, et al. Angiotensin I conversion by human and rat chymotryptic proteinases. J Invest Dermatol 1984; 83:336.
  61. Reilly CF, Schechter NB, Travis J. Inactivation of bradykinin and kallidin by cathepsin G and mast cell chymase. Biochem Biophys Res Commun 1985; 127:443.
  62. Caughey GH, Leidig F, Viro NF, Nadel JA. Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. J Pharmacol Exp Ther 1988; 244:133.
  63. Briggaman RA, Schechter NM, Fraki J, Lazarus GS. Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. J Exp Med 1984; 160:1027.
  64. Mizutani H, Schechter N, Lazarus G, et al. Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. J Exp Med 1991; 174:821.
  65. Sommerhoff CP, Caughey GH, Finkbeiner WE, et al. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol 1989; 142:2450.
  66. Mackins CJ, Kano S, Seyedi N, et al. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. J Clin Invest 2006; 116:1063.
  67. Silver RB, Reid AC, Mackins CJ, et al. Mast cells: a unique source of renin. Proc Natl Acad Sci U S A 2004; 101:13607.
  68. Le TH, Coffman TM. A new cardiac MASTer switch for the renin-angiotensin system. J Clin Invest 2006; 116:866.
  69. Abonia JP, Friend DS, Austen WG Jr, et al. Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle. J Immunol 2005; 174:7285.
  70. Boyce JA. Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev 2007; 217:168.
  71. Yokomizo T, Uozumi N, Takahashi T, et al. Leukotriene A4 hydrolase and leukotriene B4 metabolism. J Lipid Mediat Cell Signal 1995; 12:321.
  72. Church MK, el-Lati S, Caulfield JP. Neuropeptide-induced secretion from human skin mast cells. Int Arch Allergy Appl Immunol 1991; 94:310.
  73. el-Lati SG, Dahinden CA, Church MK. Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol 1994; 102:803.
  74. Church MK, et al. Functional heterogeneity of human mast cells. In: Mast cell and basophil differentiation and function in health and disease, Galli SJ, Austen KF (Eds), Raven Press, New York 1989.
  75. Murray JJ, Tonnel AB, Brash AR, et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med 1986; 315:800.
  76. Knani J, Campbell A, Enander I, et al. Indirect evidence of nasal inflammation assessed by titration of inflammatory mediators and enumeration of cells in nasal secretions of patients with chronic rhinitis. J Allergy Clin Immunol 1992; 90:880.
  77. O'Sullivan S, Dahlén B, Dahlén SE, Kumlin M. Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction. J Allergy Clin Immunol 1996; 98:421.
  78. Roberts LJ 2nd, Sweetman BJ, Lewis RA, et al. Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med 1980; 303:1400.
  79. Matsuoka T, Hirata M, Tanaka H, et al. Prostaglandin D2 as a mediator of allergic asthma. Science 2000; 287:2013.
  80. Metcalfe DD. The treatment of mastocytosis: an overview. J Invest Dermatol 1991; 96:55S.
  81. Flower RJ, Harvey EA, Kingston WP. Inflammatory effects of prostaglandin D2 in rat and human skin. Br J Pharmacol 1976; 56:229.
  82. Hardy CC, Robinson C, Tattersfield AE, Holgate ST. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med 1984; 311:209.
  83. Pugliese G, Spokas EG, Marcinkiewicz E, Wong PY. Hepatic transformation of prostaglandin D2 to a new prostanoid, 9 alpha,11 beta-prostaglandin F2, that inhibits platelet aggregation and constricts blood vessels. J Biol Chem 1985; 260:14621.
  84. Goetzl EJ. Oxygenation products of arachidonic acid as mediators of hypersensitivity and inflammation. Med Clin North Am 1981; 65:809.
  85. Raible DG, Schulman ES, DiMuzio J, et al. Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. J Immunol 1992; 148:3536.
  86. Urade Y, Hayaishi O. Prostaglandin D2 and sleep regulation. Biochim Biophys Acta 1999; 1436:606.
  87. Morrow JD, Awad JA, Oates JA, Roberts LJ 2nd. Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. J Invest Dermatol 1992; 98:812.
  88. Lewis RA, Soter NA, Diamond PT, et al. Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J Immunol 1982; 129:1627.
  89. MacGlashan DW Jr, Schleimer RP, Peters SP, et al. Generation of leukotrienes by purified human lung mast cells. J Clin Invest 1982; 70:747.
  90. Tager AM, Bromley SK, Medoff BD, et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 2003; 4:982.
  91. Taube C, Miyahara N, Ott V, et al. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. J Immunol 2006; 176:3157.
  92. Lam BK, Xu K, Atkins MB, Austen KF. Leukotriene C4 uses a probenecid-sensitive export carrier that does not recognize leukotriene B4. Proc Natl Acad Sci U S A 1992; 89:11598.
  93. Juhlin L, Hammarström S. Effects of intradermally injected leukotriene C4 and histamine in patients with urticaria, psoriasis and atopic dermatitis. Br J Dermatol 1982; 107 Suppl 23:106.
  94. Arm JP, Lee TH. Sulphidopeptide leukotrienes in asthma. Clin Sci (Lond) 1993; 84:501.
  95. Austen KF. The Paul Kallós Memorial Lecture. From slow-reacting substance of anaphylaxis to leukotriene C4 synthase. Int Arch Allergy Immunol 1995; 107:19.
  96. Miadonna A, Tedeschi A, Leggieri E, et al. Behavior and clinical relevance of histamine and leukotrienes C4 and B4 in grass pollen-induced rhinitis. Am Rev Respir Dis 1987; 136:357.
  97. Wenzel SE, Larsen GL, Johnston K, et al. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis 1990; 142:112.
  98. Taylor GW, Taylor I, Black P, et al. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet 1989; 1:584.
  99. Maltby NH, Ind PW, Causon RC, et al. Leukotriene E4 release in cold urticaria. Clin Exp Allergy 1989; 19:33.
  100. Jiang Y, Kanaoka Y, Feng C, et al. Cutting edge: Interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J Immunol 2006; 177:2755.
  101. Jiang Y, Borrelli LA, Kanaoka Y, et al. CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene dependent mitogenic responses of mast cells. Blood 2007; 110:3263.
  102. Paruchuri S, Jiang Y, Feng C, et al. Leukotriene E4 activates peroxisome proliferator-activated receptor gamma and induces prostaglandin D2 generation by human mast cells. J Biol Chem 2008; 283:16477.
  103. Triggiani M, Hubbard WC, Chilton FH. Synthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine by an enriched preparation of the human lung mast cell. J Immunol 1990; 144:4773.
  104. Imaizumi TA, Stafforini DM, Yamada Y, et al. Platelet-activating factor: a mediator for clinicians. J Intern Med 1995; 238:5.
  105. Okada S, Kita H, George TJ, et al. Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines. Am J Respir Cell Mol Biol 1997; 16:455.
  106. Prpic V, Uhing RJ, Weiel JE, et al. Biochemical and functional responses stimulated by platelet-activating factor in murine peritoneal macrophages. J Cell Biol 1988; 107:363.
  107. Czarnetzki B. Increased monocyte chemotaxis towards leukotriene B4 and platelet activating factor in patients with inflammatory dermatoses. Clin Exp Immunol 1983; 54:486.
  108. Thivierge M, Rola-Pleszczynski M. Platelet-activating factor enhances interleukin-6 production by alveolar macrophages. J Allergy Clin Immunol 1992; 90:796.
  109. Smith LJ. The role of platelet-activating factor in asthma. Am Rev Respir Dis 1991; 143:S100.
  110. Zimmerman GA, McIntyre TM, Prescott SM. Adhesion and signaling in vascular cell--cell interactions. J Clin Invest 1996; 98:1699.
  111. Stafforini DM, Satoh K, Atkinson DL, et al. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest 1996; 97:2784.
  112. Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med 2008; 358:28.
  113. Hozawa S, Haruta Y, Ishioka S, Yamakido M. Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma. Am J Respir Crit Care Med 1995; 152:1198.
  114. Gordon JR, Burd PR, Galli SJ. Mast cells as a source of multifunctional cytokines. Immunol Today 1990; 11:458.
  115. Bradding P, Okayama Y, Howarth PH, et al. Heterogeneity of human mast cells based on cytokine content. J Immunol 1995; 155:297.
  116. Bradding P, Feather IH, Wilson S, et al. Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. J Immunol 1993; 151:3853.
  117. Bradding P, Feather IH, Howarth PH, et al. Interleukin 4 is localized to and released by human mast cells. J Exp Med 1992; 176:1381.
  118. Jaffe JS, Glaum MC, Raible DG, et al. Human lung mast cell IL-5 gene and protein expression: temporal analysis of upregulation following IgE-mediated activation. Am J Respir Cell Mol Biol 1995; 13:665.
  119. Bressler RB, Lesko J, Jones ML, et al. Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation. J Allergy Clin Immunol 1997; 99:508.
  120. Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 1990; 346:274.
  121. Gordon JR, Galli SJ. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. J Exp Med 1991; 174:103.
  122. Echtenacher B, Männel DN, Hültner L. Critical protective role of mast cells in a model of acute septic peritonitis. Nature 1996; 381:75.
  123. Malaviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 1996; 381:77.
  124. Suto H, Nakae S, Kakurai M, et al. Mast cell-associated TNF promotes dendritic cell migration. J Immunol 2006; 176:4102.
  125. Klein LM, Lavker RM, Matis WL, Murphy GF. Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. Proc Natl Acad Sci U S A 1989; 86:8972.
  126. Wegner CD, Gundel RH, Reilly P, et al. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science 1990; 247:456.
  127. McLachlan JB, Hart JP, Pizzo SV, et al. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nat Immunol 2003; 4:1199.
  128. Qu Z, Liebler JM, Powers MR, et al. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol 1995; 147:564.
  129. Alam R. Chemokines in allergic inflammation. J Allergy Clin Immunol 1997; 99:273.
  130. Möller A, Lippert U, Lessmann D, et al. Human mast cells produce IL-8. J Immunol 1993; 151:3261.
  131. Gurish MF, Boyce JA. Mast cells: ontogeny, homing, and recruitment of a unique innate effector cell. J Allergy Clin Immunol 2006; 117:1285.
  132. Nilsson G, Svensson V, Nilsson K. Constitutive and inducible cytokine mRNA expression in the human mast cell line HMC-1. Scand J Immunol 1995; 42:76.
  133. Nigrovic PA, Binstadt BA, Monach PA, et al. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 2007; 104:2325.