MAST CELLS, THE EFFECTOR CELLS OF IgE-MEDIATED ALLERGY
DOI:
https://doi.org/10.58395/292bv823Keywords:
Mast cells, Degranulation, IgE-mediated allergy, Basophil activation test, Mast cell activation testAbstract
Background: Mast cells, are the primary responder cells of IgE-mediated allergy and while extensive research has been done to elucidate their precise structural and functional characteristics, mast cells are a type of tissue resident cell which makes their isolation and use for various research and diagnostic procedures in the field of allergy and immunology very complicated. Recently, attempts have been made to devise a method measuring mast cell degranulation through allergen stimulation for allergy diagnosis – Mast cell activation test (MAT). The aim of this article is to summarize existing knowledge on mast cells, the MAT, and the related Basophil activation test (BAT) on which the MAT is based on.
Methods: We analyzed data from 51 relevant articles.
Results: We made an extensive literature review of available data on the cytology, biochemistry and role of mast cells in the pathogenesis of allergic diseases-anaphylaxis, allergic rhinitis, and bronchial asthma, as well as available data on the MAT andhow it compares to the BAT.
Conclusion: While much key information is available on mast cells, further research is required to expand on their function and role in allergy. Further research is needed to adequately compare MAT and BAT and create standardized protocols for the application of MAT in clinical practice and allergy research.
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References
1. St. John, A.L., Rathore, A.P.S. & Ginhoux, F. New perspectives on the origins and heterogeneity of mast cells. Nat Rev Immunol. 2023, 23: 55–68. https://doi.org/10.1038/s41577-022-00731-2.
2. Bischoff, S. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol. 2007; 7: 93–104. https://doi.org/10.1038/nri2018.
3. Harvima IT, Nilsson G. Mast cells as regulators of skin inflammation and immunity. Acta Derm Venereol 2011; 91: 644–650. https://doi.org/10.2340/00015555-1197.
4. Crivellato E, Travan L, Ribatti D. The phylogenetic profile of mast cells. Methods Mol Biol. 2015; 1220: 11-27. https://doi.org/10.1007/978-1-4939-1568-2.
5. St. John AL, Rathore APS, Ginhoux F. New perspectives on the origins and heterogeneity of mast cells. Nat Rev Immunol 2023; 23: 55–68. https://doi.org/10.1038/s41577-022-00731-2.
6. Dahlin JS, Hallgren J. Mast cell progenitors: Origin, development and migration to tissues. Mol Immunol, 2015; 63, 1: 9-17. https://doi.org/10.1016/j.molimm.2014.01.018.
7. Schwartz LB. Analysis of MCT and MCTC Mast Cells in Tissue. In: Krishnaswamy G., Chi DS. (eds) Mast Cells. Methods in Molecular Biology, 2006; vol 315. Humana Press. https://doi.org/10.1385/1-59259-967-2:05.
8. Gurish MF, Austen KF. Developmental origin and functional specialization of mast cell subsets. Immunity 2012; 37: 25–33. https://doi.org/10.1016/j.immuni.2012.07.003.
9. Yong L.C.J. The mast cell: origin, morphology, distribution, and function. Experimental and Toxicologic Pathology, 1997; 49, 6: 409-424. https://doi.org/10.1016/S0940-993(97)80129-7.
10. Schwartz LB, Irani AM, Roller K, Castells, MC, Schechter NM. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 1987; 138:2611-2615. PMID: 3549903.
11. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr 2007; 85: 1185-1196. https://doi.org/10.1093/ajcn/85.5.1185.
12. Mandola A, Nozawa A, Eiwegger T. Histamine, histamine receptors, and anti-histamines in the context of allergic responses. Lympho Sign Journal 2019; 6: 35–51. https://doi.org/10.14785/lymphosign-2018-0016.
13. Togias A. H1-receptors. J Allergy Clin Immuno 2003; 112, 4, S60 - S68. https://doi.org/10.1016/S0091-6749(03)01878-5.
14. Monczor F, Fernandez N. Current Knowledge and Perspectives on Histamine H1 and H2 Receptor Pharmacology: Functional Selectivity, Receptor Crosstalk, and Repositioning of Classic Histaminergic Ligands. Mol Pharmacol. 2016 Nov;90(5):640-648. https://doi.org/10.1124/mol.116.105981.
15. Schlicker, E., Kathmann, M. (2016). Role of the Histamine H3 Receptor in the Central Nervous System. In: Hattori, Y., Seifert, R. (eds) Histamine and Histamine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 241. Springer, Cham. https://doi.org/10.1007/164_2016_12.
16. Dong H, Zhang X, Qian Y. Mast cells and neuroinflammation. Med Sci Monit Basic Res. 2014; Dec 21;20:200-6. https://doi.org/10.12659/MSMBR.893093.
17. Zampeli E, Tiligada E. The role of histamine H4 receptor in immune and inflammatory disorders. Br J Pharmacol. 2009 May;157(1):24-33. https://doi.org/10.1111/j.1476-5381.2009.00151.x.
18. Hellman L, Akula S, Fu Z, Wernersson S. Mast cell and basophil granule proteases - In Vivo targets and function. Front. Immunol. 2022; 13: 918305. https://doi.org/10.3389/fimmu.2022.918305.
19. Stone KD., Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010; 125:S73-80. https://doi.org/10.1016/j.jaci.2009.11.017.
20. Lafleur MA, Werner J, Fort M, Lobenhofer E K, Balazs M, & Goyos A. MRGPRX2 activation as a rapid, high-throughput mechanistic-based approach for detecting peptide-mediated human mast cell degranulation liabilities. Journal of Immunotoxicology, 2020:17(1); 110–121. https://doi.org/10.1080/1547691X.2020.1757793.
21. Thapaliya M, Chompunud Na Ayudhya C, Amponnawarat A, Roy S, Ali H. Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases. Curr Allergy Asthma Rep. 2021 Jan 4; 21(1):3. https://doi.org/10.1007/s11882-020-00979-5.
22. Sandig H, Bulfone-Paus S. TLR signaling in mast cells: common and unique features. Front Immunol. 2012 Jul 4; 3: 185. https://doi.org/10.3389/fimmu.2012.00185.
23. Mendoza RP, Anderson CC, Fudge DH, Roede JR, Brown JM. Metabolic Consequences of IgE- and Non-IgE-Mediated Mast Cell Degranulation. J Immunol. 2021 Dec 1;207(11):2637-2648. https://doi.org/10.4049/jimmunol.2001278.
24. Tuma RS. The degranulation two-step. J Cell Biol. 2005 Jul 4;170(1):9. https://doi.org/10.1083/jcb1701iti5.
25. Gaudenzio N, Sibilano R, Marichal T, Starkl P, Reber LL, Cenac N et al. Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest. 2016; 126 (10): 3981–3998. https://doi.org/10.1172/JCI85538.
26. Xiang Z, Block M, Löfman C, Nilson G. IgE-mediated mast cell degranulation and recovery monitored by time-lapse photography J. Allergy Clin. Immunol. 2001; 108: 116-121. https://doi.org/10.1067/mai.2001.116124.
27. Moon TC, Befus AD, Kulka M. Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol. 2014 Nov 14; 5: 569. https://doi.org/10.3389/fimmu.2014.00569.
28. Kashiwakura J, Otani IM, Kawakami T. Monomeric IgE and mast cell development, survival and function. Adv Exp Med Biol. 2011; 716: 29-46. https://doi.org/10.1007/978-1-4419-9533-9_3.
29. Cruse G, Kaur D, Yang W, Duffy SM, Brightling CE, Bradding P. Activation of human lung mast cells by monomeric immunoglobulin E. Eur Respir J 2005; 25: 858–863. https://doi.org/10.1183/09031936.05.00091704.
30. Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol 2016; 138: 700-710. https://doi.org/10.1016/j.jaci.2016.04.051
31. Metcalfe DD, Peavy RD, Gilfillan AM. Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin Immunol. 2009 Oct; 124 (4):639-46; quiz 647-8. https://doi.org/10.1016/j.jaci.2009.08.035.
32. Zoabi Y, Levi-Schaffer F, Eliashar R. Allergic Rhinitis: Pathophysiology and Treatment Focusing on Mast Cells. Biomedicines 2022, 10, 2486. https://doi.org/10.3390/biomedicines10102486.
33. Méndez-Enríquez E., Hallgren J. Mast Cells and Their Progenitors in Allergic Asthma. Front. Immunol. 2019; 10: 821. https://doi.org/10.3389/fimmu.2019.00821.
34. Poto R, Criscuolo G, Marone G, Brightling CE, Varricchi G. Human Lung Mast Cells: Therapeutic Implications in Asthma. Int J Mol Sci. 2022 Nov 21; 23(22): 14466. https://doi.org/10.3390/ijms232214466.
35. Baran J, Sobiepanek A, Mazurkiewicz-Pisarek A, Rogalska M, Gryciuk A, Kuryk L, Abraham SN, Staniszewska M. Mast Cells as a Target-A Comprehensive Review of Recent Therapeutic Approaches. Cells. 2023; Apr 19;12(8):1187. https://doi.org/10.3390/cells12081187.
36. Payne V, Kam PCA. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia. 2004; 59: 695-703. https://doi.org/10.1111/j.1365-2044.2004.03757.x
37. Asai H, Yamamoto R, Kuromiya K, Takamura R, Jin W, Kurosaki H, Fukuishi N. A Rapid and Sensitive Determination of Histamine in Mast Cells Using a Didansyl Derivatization Method. Int Arch Allergy Immunol. 2022;183(10):1050-1055. https://doi.org/10.1159/000525588.
38. Jensen BM, Bartko E, Baumann K, Skov P. Measuring Histamine and Cytokine Release from Basophils and Mast Cells. Chapter In book: Basophils and Mast Cells. 2020; 247-262, https://doi.org/10.1007/978-1-0716-0696-4_21.
39. Orfao A, Escribano L, Villarrubia J, Velasco JL, Cerveró C, Ciudad J, Navarro JL, San Miguel JF. Flow cytometric analysis of mast cells from normal and pathological human bone marrow samples: identification and enumeration. Am J Pathol. 1996 Nov; 149 (5):1493-9. PMID: 8909239.
40. Ng DP. How can flow cytometry identify normal and abnormal mast cells? International Clinical Cytometry Society. 2018.
41. Knol EF, Mul FP, Jansen H, Calafat J, Roos D. Monitoring human basophil activation via CD63 monoclonal antibody 435. J Allergy Clin Immunol. 1991; 88 (3 Pt 1):328-338. https://doi.org/10.1016/0091-6749(91)90094-5.
42. MacGlashan D Jr. Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes. Clin Exp Allergy. 2010 Sep;40(9):1365-77. https://doi.org/10.1111/j.1365-2222.2010.03572.x.
43. Ebo DG, Bridts CH, Mertens CH, Sabato V. Principles, potential, and limitations of ex vivo basophil activation by flow cytometry in allergology: a narrative review. J Allergy Clin Immunol. 2021; 147 (4): 1143-1153. https://doi.org/10.1016/j.jaci.2020.10.027.
44. Bahri R, Bulfone-Paus S. Mast Cell Activation Test (MAT). Methods Mol Biol. 2020; 2163: 227-238. https://doi.org/10.1007/978-1-0716-0696-4_19.
45. Zbären N, Brigger D, Bachmann D, Helbling A et al. A novel functional mast cell assay for the detection of allergies. J of Allergy and Clin Immunol. 2022; 149: 1018-30. https://doi.org/10.1016/j.jaci.2021.08.006.
46. Elst J, van der Poorten MM, Van Gasse AL, et al. Mast cell activation tests by flow cytometry: a new diagnostic asset? Clin Exp Allergy. 2021; 51 (11):1482-1500. https://doi.org/10.1111/cea.13984.
47. Ebo DG, Bahri R, Tontini C, Van Gasse AL, Mertens C, Hagendorens MM, Sabato V, Elst J. Mast cell versus basophil activation test in allergy: Current status. Clin Exp Allergy. 2024 Jun;54 (6): 378-387. https://doi.org/10.1111/cea.14487.
48. Torres MJ, Padial A, Mayorga C, Fernández T, Sanchez-Sabate E, Cornejo-García JA, et al. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Clin Exp Allergy. 2004;34:1768–75.
49. Rouzaire P, Nosbaum A, Denis L, Bienvenu F, Bérard F, Cozon G, et al. Negativity of the basophil activation test in quinolone hyper-sensitivity: a breakthrough for provocation test decision-making. Int Arch Allergy Immunol. 2012; 157:299–302.
50. Santos AF, Lack G. Basophil activation test: food challenge in a test tube or specialist research tool? Clin Transl Allergy. 2016 Mar 15;6:10. https://doi.org/10.1186/s13601-016-0098-7. PMID: 26981234; PMCID: PMC4791855.
51. Hoffmann, Hans Jürgen et al. Pros and Cons of Clinical Basophil Testing (BAT). Current allergy and asthma reports. 2016; 16: 8 - . https://doi.org/10.1007/s11882-016-0633-6
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Copyright (c) 2025 Assoc. Prof. D-r Georgi Nikolov, Assoc. Prof. Radoslava Emilova , Yana Todorova, Diana Milcheva, Prof. Maria Nikolova (Author)
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