Human mast cells

Synthesis. Histamine [51-45-6] 2-(4-imidazolyl)ethylarnine (1) is formed by decarboxylation of histidine by the enzyme L-histidine decarboxylase (Fig. 1). Most histamine is stored preformed in cytoplasmic granules of mast cells and basophils. In humans mast cells are found in the loose connective tissue of all organs, especially around blood and lymphatic vessels and nerves. These cells are most abundant in the organs expressing allergic diseases the skin, respiratory tract, and gastrointestinal tract. 

The mast cell stabilizers currently for ophthalmic use are nedocromil and pemirolast. These drugp are used for the prevention of eye itching caused by allergic conjunctivitis. The mast cell stabilizers act by inhibiting the antigen-induced release of inflammatory mediators (eg, histamine) from human mast cells. 

Adding another layer of complexity to the regulation of mast cell activation levels in vivo is the observation that activated mast cells can respond to, and in some cases produce, a myriad of mediators that may serve to amplify FceRI-induced responses. For example, stem cell factor (SCF), the ligand for KIT, both can enhance FceRI-dependent activation of mouse or human mast cells and, under certain circumstances, can directly induce mast cell degranulation [6, 25, 62]. Thus, elevated SCF levels and/or activating KIT mutations (such as those that occur in mastocytosis) may exacerbate mast cell-driven reactions. Indeed, patients (both adult and children) with extensive skin disease associated with mastocytosis are at increased risk to develop severe anaphylaxis [63]. Moreover, it was recently reported that cases of idiopathic anaphylaxis are... 

Sander LE. Frank SP, Bolat S, Blank U, Galli T. Bigalke H. Bischoff SC, Lorentz A Vesicle-associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells. Eur J Immunol 2008 38 855-863. 

Bansal G, DiVietro JA, Kuehn HS, Rao S, Nocka KH, Gilfillan AM, Druey KM RGS13 controls G protein-coupled receptor-evoked responses of 56 human mast cells. J Immunol 2008 181 7882-7890. 

Matsuda K, Piliponsky AM, likura M, Nakae S, Wang EW, Dutta SM, Kawakami T, Tsai M, Galli SJ Monomeric IgE enhances human mast cell chemokine production IL-4 augments and dexam-ethasone suppresses the response. J Allergy Clin Immunol 2005 116 1357-1363. 

Costa JJ, Demetri GD, Harris TJ. Dvorak AM. Hayes DF, Merica EA, Menchaca DM. Gringeri AJ. Schwartz LB, Galli SJ Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med 1996 183 2681-2686. 

Patella V, Ciccarelli A, Lamparter-Schummert B. de Paulis A, Adt M, Marone G Heterogeneous effects of protamine on human mast cells and basophils. Br J Anaesth 1997 78 724. 

Schechter NM. Irani AM. Sprows JL. Abernethy J. Wintroub B, Schwartz LB Identification of a cathe-psin G-like proteinase in the MC, - type of human mast cell. J Immunol 1990 145 2652. 

Tkaczyk C, Horej si V, Iwaki S, et al NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation. Blood 2004 104 207-214. 17... 

Akin C. Brockow K. D Ambrosio C. et al Effects of tyrosine kinase inhibitor SXI571 on human mast cells bearing wild-type or mutated c-kit. Exp Hem-atol 2003 31 686-692. 

Tryptase is at the present moment the main clinical marker for anaphylaxis and mastocytosis. There are two major human mast cells tryptases, a- and (3-tryptase, encoded by two genes located at chromosome 16. The haploid genotype for tryptase is (3a or (3(3.25% of individuals are a-tryptase-deficient a-tryptase shows a 90% amino acid sequence identity with (3-tryptase. 

Schwartz LB, Yunginger JW, Miller J, Bokhari R, Dull D Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 1989 83 1551-1555. 

Price KS, Friend DS, Mellor EA, De Jesus N, Watts GF, Boyce JA. CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. Am J Respir Cell Mol Biol 2003 28(4) 420-427. 

He SH, Xie H, Zhang XJ, Wang XJ. Inhibition of histamine release from human mast cells by natural chymase inhibitors. Acta Pharmacol Sin. 2004 25 822-826. 

Bhattacharyya, S.P., Drucker, I., Reshef, T., Kirshenbaum, A.S., Metcalfe, D.D. and Mekori, Y.A. (1998) Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact. Journal of Leukocyte Biology 63, 337-341. 

Torn, H., Pawankar, R., Ra, C., Yata, J. and Nakahata, T. (1998) Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking enhanced ILrl3 production by IU4-primed human mast cells. Journal of Allergy and Clinical... 

Mellor, E. A., Frank, N., Soler, D., et al.. (2003) Expression of the type 2 receptor for cysteinyl leukotrienes (CysLT2R) by human mast cells functional distinction from CysLTlR. Proc. Natl. Acad. Sci. U. S. Am. 100,11589-11593. 

By a negative feedback control mechanism mediated by H2 receptors, histamine appears to modulate its own release and that of other mediators from sensitized mast cells in some tissues. In humans, mast cells in skin and basophils show this negative feedback mechanism lung mast cells do not. Thus, histamine may act to limit the intensity of the allergic reaction in the skin and blood. 

The Receptor Responsible for Adenosine Augmentation of Mediator Release from Human Mast Cells Is Not the A3 Receptor... 

At about the time that the efforts of the chemists to synthesise selective A3 antagonists had begun to bear fruit (1995/1996), the assumption implicit in our concept that human mast cells would behave like those of the rodent was called into serious question. The first (and key) observations came from Feoktistov and Biaggioni (1995) who provided evidence that in the human mast cell line, HMC-1 (which although derived from a patient with mast cell leukaemia shows some biochemical characteristics similar to the mast cells of the lung (Feoktistov et al. 1998)), the A2B receptor and not the A3 receptor is responsible for the potentiation of phorbol... 

Ezeamuzie Cl, Philips E (2003) Positive coupling of atypical adenosine A3 receptors on human eosinophils to adenylyl cyclase. Biochem Biophys Res Commun 300 712-718 Feoktistov I, Biaggioni I (1995) Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J Clin Invest... 

Feoktistov I, Biaggioni I (1998) Pharmacological characterization of adenosine A2B receptors studies in human mast cells coexpressing A2A and A2B adenosine receptor subtypes. Biochem Pharmacol 55(5) 627-633... 

Bradding P, Roberts JA, Britten KM, Montefort S, et al. 1994. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways Evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 10 471—480. 

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