The Mast Cells Volume 51- Issue 2

Wilairat Leeanansaksiri^1* and Chavaboon Dechsukhum²

• ¹School of Preclinic, Institute of Science, Suranaree University of Technology, Thailand
• ²School of Pathology, Institute of Medicine, Suranaree University of Technology, Thailand

Received: June 06, 2023;   Published: June 27, 2023

*Corresponding author: : Wilairat Leeanansaksiri, School of Preclinic, Institute of Science, Suranaree University of Technology, Thailand

DOI: 10.26717/BJSTR.2023.51.008080

Abstract PDF

Mast cell is one of the important cells in the immune system. It is derived from multipotent hematopoietic progenitor cells. The mast cell produces a number of cytokines to augment immune responses, growth, and differentiation of other cells. This cell also exhibits multifunctional roles in health and diseases. This review provides board overview of the mast cell including mast cell discovery and development, characteristics of mast cells, mast cell activation, regulation and functions in health and diseases. Understanding hallmark of the mast cell will benefit the development of therapeutic approaches of the mast cell in the future.

Abbreviations: CTMCs: Connective Tissue Mast Cells; MMCs: Mucosal Mast Cells; SCF: Stem Cell Factor; SYK: Spleen- Associated Tyrosine Kinase; BTK: Bruton’s Tyrosine Kinase

Mast cells are bone marrow derived hemopoietic cells (Kitamura, et al. [1-3]). The mast cell is one of the important cells in the immune system. It is derived from multipotent hematopoietic progenitor cells. The mast cell produces a number of cytokines to augment immune responses, growth, and differentiation of other cells. This cell also exhibits multifunctional roles in innate immunity against bacterial and parasite infections, immediate and delay hypersensitivity reactions, inflammation, fibrosis, autoimmune pathology neoplasia, wound healing and angiogenesis (Mekori, et al. [4-9]). Unlike the other hematopoietic cells, mature mast cells maintain their ability to proliferate under normal conditions (Metcalfe, et al. [7]). Mast cell progenitors express many transcription factors and need GATA-2, PU.1 transcription factors for their survival and development (Tsai, et al. [10,11]).

The mast cell was first identified as a cell containing metachromatic properties in connective tissue by Paul Ehrlich who believed that overfeeding of this cell generated inclusion bodies inside the cell (Ehrlich, et al. [12,13]). Rodent mast cells can be categorized into two classes, connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), based on their histochemical heterogeneity (Enerback, et al. [14-16]). Mucosal mast cells stained with Alcian blue because of the predominant chondroitin sulfate proteoglycan in the granule contents. On the other hand, connective tissue mast cells containing heparin as a major proteoglycan in the granule stained with Safanin but not Alcian blue. CTMCs are distributed in the entire connective tissues of skin, in the peritoneal cavity, adjacent to blood vessels and to peritoneal nerves, whereas MMCs are present in the lung and the intestinal lamina propia (Aldenborg, et al. [17,18]). These two subtypes of mast cells have some different functions, e.g. MMC proliferate profoundly during T-cell dependent immune responses to certain intestinal parasites (Schmitt, et al. [19,20]), while CTMC exhibit a normal proliferation profile (Aldenborg, et al. [17]). In humans, there are three subsets of mast cells that have been characterized:

1. MC_T, which expresses tryptase and resides primarily in the alveolar septa of the lung and in the small intestinal mucosa;

2. MC_TC, which expresses tryptase, chymase, carboxypeptidase A (CPA) and cathepsin G and resides primarily in the skin and in the small intestinal submucosa;

3. MC_c, which expresses chymase but lacks tryptase (Schwartz, et al. [21-26] Dahlin et al., 2020).

Based on tissue location, the human MCT is related to the rodent MMC and the MCTC is related to the rodent CTMC. In the murine system, stem cell factor (SCF) and IL-3 are essential for mast cell maturation while human mast cells need only SCF but not IL-3 for their development (Huang, et al. [27-33]). The recently described MC_c subset can also be differentiated from normal human hematopoietic stem cells in vitro (Li, et al. [24]) Murine bone marrow cultured in SCF and IL-3 gives rise to populations of mast cells that most resemble the connective tissue phenotype (Tsai, et al. [31]). CD34⁺ stem cells from human cord blood, peripheral blood (Rottem, et al. [34,35]) and fetal liver (Irani, et al. [36]) in the presence of SCF will differentiate into human mast cells. In addition to IL-3 and SCF, the proliferation and differentiation of mast cells can be enhanced by adding other growth factor including IL-4, IL-9, IL-10 and nerve growth factor (Hultner, et al. [37-39]). The mast cell progenitor first appears in the yolk sac at day 10 of gestation. Unlike mast cell precursors in fetal liver and bone marrow, mast cell progenitors in yolk sac are uni-potential for mast cells in the presence of SCF and IL-3. Mast cell precursors express the high affinity IgE receptor (FcεRI) and FcγRII/III before granulation (Rottem, et al. [40-44]). Mast cells are believed to leave the bone marrow as non-granulated mast cells and complete their differentiation as mature mast cells in mucosal and connective tissue where they differentiate into tissue- specific mast cells (Dahlin, et al. 2020).

Mature mast cells express a diverse array of cell surface antigens. The most important are c-Kit (a receptor for SCF which promotes mast cell maturation, survival and adhesion) and the FcεRI which plays a crucial role in IgE-mediated allergy and also in mast cell maturation (Cop, et al. [45-47]). It has been reported that bone marrow cultured in the presence of IL-3 exhibits the mRNA expession of the three subunits α, β and γ of FcεRI in a week and this expression continues to increase over 3 weeks during mast cell development (Rottem, et al. [40,41]). These studies also show that the cells containing low FcεRI often contain few granules and thus lack the morphologic characteristics of mature mast cells. In addition, the FcεRI positive cells have proliferative potential but are slower than the mast cell progenitors that do not yet express FcεRI. These findings suggest that FcεRI expression on mast cells is a marker of terminal differentiation, and this receptor expression may also provide cells to respond to the growth factors and other stimuli before they exhibit granule maturation and are morphologically recognized as mature mast cells (Rottem, et al. [40]). Mature differentiated mast cells maintain their CFU-mast characteristic feature (Metcalfe, et al. [7]) which is capable of continuing proliferation under normal conditions. This unique characteristic of mast cells distinguishes them from other hematopoietic cells, e.g. basophils, neutrophils and eosinophils. Adhesion of mast cells to extracellular matrix compartments is mediated by many adhesion molecule receptors expressed on the cell surface of mast cells such as laminin, fibronectin, VLA-3, VLA-4 and VLA-5, vitronectin receptors (Columbo, et al. [48-50]). Cross-linking of FcεRI on BMMC has been reported to promote the attachment, and this adherence occurred at a lower dose of antigen challenge than that required for histamine release (Thompson, et al. [51]). Culture of mast cells with TGF-β enhances IgE-mediated adhesion of mast cells to laminin (Mecalfe, et al. [7]), and SCF also promotes the adhesion of IL-3-dependent BMMC to fibronectin in a dose dependent manner (Dastych, et al. [52]). However, IL-1, IL-2, IL-3, IL-4, IFN-γ, TNF and GM-CSF have no activation effect on the adhesion of mast cell to laminin (Thompson, et al. [51]). Mast cells also have been found to interact with lymphocytes in inflamed tissue, during bacterial and parasitic infections (Friedman, et al. [47,53-55]).

Mast cell activation can be achieved via FcεRI dependent and FcεRI independent pathways (Cop, et al. [45,47]). The activation of mast cell through FcεRI dependent pathway is started by cross linking of FcεRI receptors after interaction with IgE bound antigen. Many compound and cytokines are also known as mast cell activators by FcεRI independent pathway such as compound 48/80 (Ortner, et al. [56]), mastoparan, polymyxin B and other basic amino acid polymers (Lagunoff, et al. [57]), Rab3A (Oberhauser, et al. [58]), IL-1, IL-3, and GM-CSF platelet factor 4 and SCF (Alam, et al. [59-63]), C3a, C4a, C5a (Demopoulos, et al. [64,65]), dextrans and lectins (Lagunoff et al. [57]). After activation mast cells release mediators form granules (histamin, mast cell proteinase MMCP1-5, tryptase MMCP6-7, carboxypeptidase A or CPA). Activated mast cells also synthesize and release new mediators from cyclooxygenase products (prostaglandins and thromboxanes) and lipoxygenases (leukotrienes, LTs). In addition, mast cells generate a variety of cytokines such as TNF-α, IFN-γ, GM-CSF, MIP-1β, T-cell activation gene (TCA)-3, IL-2, IL-3, IL- 4, IL-5, Il-6, IL-10, IL-12, IL-13 (Burd, et al. [54,66-70] Dahlin et al. 2021, Levi-Schaffer, et al. [47,71])

The rate of cell proliferation and cell death, which is often due to apoptosis, are the key regulators in cell homeostasis (Arends, et al. [72]). In mast cells, IL-3 is important for early mast cell proliferation and SCF is important for mast cell differentiation. SCF also promotes mast cell adhesion to the extracellular matrix (Tsai, et al. [31,52,73]). Mast cells undergo apoptosis after removing IL-3. However, SCF (but not insulin growth factor and NGF) can prevent apoptosis in both in vitro and in vivo systems (Mekori, et al. [74,75]). Many therapeutic approaches were developed to inhibit mast cell activation via blocking IgE receptor (FcεRI) activation and inhibit signaling transduction pathway involving mast cell degranulation and mediator release e.g. Bruton's tyrosine kinase (BTK) and spleen- associated tyrosine kinase (SYK). Inhibitors of BTK or SYK down regulate the degranulation of human mast cells induced via FcεRI (Dahlin et al. 2021).

Mast cells perform multiple biological functions such as innate immunity against bacterial and parasite infections, immediate and delayed hypersensitivity reactions, inflammation, fibrosis, autoimmune pathology neoplasia, wound healing, angiogenesis (Mekori, et al. [4-7]). Mast cells can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, mast cells indeed mediate acute inflammatory responses such as those evident in allergic reactions. In addition, mast cells participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. Moreover, mast cells release several cytokines to recruit other immune effector cells to the infection area which induced many inflammatory disorders of host tissues. Mast cell also exhibit pathological roles in autoimmune diseases including rheumatoid arthritis and chemokines including CXCL12, CCL2, CCL3, CCL4, and CCL5 leading to tissue destruction (De Filippo, et al. [76-78]). The control of mast cell activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, mast cells contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells (Anna Sobiepanek, et al. 2022) (Krystel-Whittemore M, et al. [79]).

Mast cell exerts many biological roles in both innate and adaptive immune responses which affect human health and diseases. Understanding hallmark of the mast cell development, characteristics, activation, regulation and functions in health and diseases can benefit the development of therapeutic approaches of the mast cell in the future.

We would like to thank Suranaree University of Technology, Thailand for supporting this manuscript.

1. Kitamura Y, Hatanaka K (1978) Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52(2): 447-452.
2. Kitamura Y, Yokoyama M, Matsuda H, Ohno T, Mori KJ (1981) Spleen colony- forming cell as common precursor for tissue mast cells and granulocytes. Nature 291(5811): 159-160.
3. Sonoda T, Kitamura Y, Haku Y, Hara H, Mori KJ, et al. (1983) Mast cell precursors in various hematopoietic colonies of mice produced in-vivo and in-vitro. BrJ Haematol 53: 611-620.
4. Mekori YA, Metcalfe DD (2000) Mast cells in innate immunity. Immunol Rev 173: 131-140.
5. Galli SJ, Maurer M, Lantz CS (1999) Mast cells as sentinels of innate immunity. Curr Opin Immunol 11(1): 53-59.
6. Galli SJ (2000) Mast cells and basophils. Curr Opin Hematol 7: 32-39.
7. Metcalfe DD, Baram D, Mekori YA (1997) Mast cells. Physiol Rev 77: 1033-1079.
8. Voehringer D (2013) Protective and pathological roles of mast cells and basophils. Nat Rev Immunol 13: 362-375.
9. Jiménez M, Cervantes-García D, Córdova-Dávalos LE, Pérez-Rodríguez MJ, Gonzalez-Espinosa C, et al. (2021) Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles. Front Immunol 12: 685865.
10. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, et al. (1994) An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371: 221-226.
11. Dahlin J, Hallgren J (2015) Mast cell progenitors: Origin, development and migration to tissues. Mol Immunol 63(1): 9-17.
12. Ehrlich P (1878) Beitrage zur Theorie und Praxis der histologischen Farbung. Leipzig: Leipzig University.
13. Ehrlich P (1879)        Uber             die                 specifischen                    Granulatoinen               des                Arch Anat Physiol Phys

Abt 571-577.

14. Enerback L (1966b) Mast cells in rat gastrointestinal mucosa. Dye-binding and metachromatic properties. Acta Pathol Microbiol Scand 66(3): 303-312.
15. Enerback L (1966a) Mast cells in rat gastrointestinal mucosa. I. Effects of fixation. Acta Pathol Microbiol Scand 66(3): 289-302.
16. Dahlin JS, Maurer M, Metcalfe DD, Pejler G, Sagi-Eisenberg R, et al. (2022) The ingenious mast cell: Contemporary insights into mast cell behavior and function. Allergy 77(1): 83-99.
17. Aldenborg F, Enerback L (1985) Thymus dependence of connective tissue mast cells: a quantitative cytofluorometric study of the growth of peritoneal mast cells in normal and athymic rats. Int Arch Allergy Appl Immunol 78(3): 277-282.
18. Bienenstock J, Befus AD, Pearce FL, Denburg JA, Goodacre R (1982) Mast cell heterogeneity: derivation and function, with emphasis on the intestine. J Allergy Clin Immunol 70(6): 407-412.
19. Schmitt E, Fassbender B, Beyreuther K, Spaeth E, Schwarzkopf R, et al. (1987) Characterization of a T cell-derived lymphokine that acts synergistically with IL 3 on the growth of murine mast cells and is identical with IL 4. Immunobiology 174: 406-419.
20. Mayrhofer G, Fisher R (1979) Mast cells in severely T cell-depleted rats and the response to infestation with Nippostrongylus brasiliensis. Immunology 37: 145-152.
21. Schwartz LB, Foley JV, Austen KF, Soter NA, Shepard R, et al. (1985) Localization of tryptase to human cutaneous mast cells and keratinocytes by immunofluorescence and immunoperoxidase cytochemistry with monoclonal antitryptase antibody. J Allergy Clin Immunol 76: 182-188.
22. Irani A-MA, Goldstein SM, Wintroub BU, Bradford T, Schwartz LB (1991) Human mast cell carboxypeptidase: Selective localization to MCTC cells. Immunol 147(1): 247-253.
23. Weidner N, Austen KF (1993) 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 189: 156-162.
24. Li L, Meng XW, Krilis SA (1996) Mast cells expressing chymase but not tryptase can be derived by culturing human progenitors in conditioned medium obtained from a human mastocytosis cell strain with c-kit ligand. J Immunol 156: 4839-4844.
25. Dwyer DF, Ordovas-Montanes J, Allon SJ, Kathleen M Buchheit, Marko Vukovic, et al. (2021) Human airway mast cells proliferate and acquire distinct inflammationdriven phenotypes during type 2 inflammation. Sci Immunol 6(56): eabb7221.
26. Andersson CK, Mori M, Bjermer L, Lofdahl CG, Erjefalt JS (2010) Alterations in lung mast cell populations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 181(3): 206-217.
27. Huang E, Nocka E, Beir DR, Chu T-Y, Buck J, et al. (1990) The hematopoietic growth factor kl is encoded by the sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 638(1): 225-233.
28. Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, et al. (1990a) Primary structure and functional expression of rat and human stem cell factor DNA's. Cell 63: 203-211.
29. Matsui Y, Zsebo KM, Hogan BLM (1990) Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c-kit. Nature 347: 667-669.
30. Nocka K, Buck J, Levi E, Besmer P (1990) Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO J 9: 3287-3294.
31. Tsai M, Takeishi T, Thompson H, Langley KE, Zsebo KM, et al. (1991) Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. Proc Natl Acad Sci 88: 6382-6386.
32. Huff TF, Lantz CS (1997) Culture of murine mast cells. In: Immunology Methods Manual. In: I Lefkovits (Edt.)., Academic Press, London, pp. 1391-1407.
33. Valent P, Besemer J, Sillaber C, Butterfield JH, Eher R, et al. (1990) Failure to detect IL-3-binding sites on human mast cells. J Immunol 145: 3432-3437.
34. Rottem M,Okada T, Goff JP, Metcalfe DD (1994) Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population. Blood 84: 1-8.
35. Valent P, Spanblöchl E, Sperr WR, Sillaber C, Zsebo, et al. (1992) Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture. Blood 80: 2237-2245.
36. Irani AA, Craig SS, Nilsson G, Ishizaka T, Schwartz LB (1992) Characterization of human mast cells developed in vitro from fetal liver cells cocultured with murine 3T3 fibroblasts. Immunology 77(1): 136-143.
37. Hultner L, Moeller J (1990) Mast cell growth-enhancing activity (MEA) stimulates interleukin 6 production in a mouse bone marrow-derived mast cell line and a malignant subline. Exp Hematol 18(8): 873-877.
38. Thompson Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, et al. (1991) Interleukin 10: A novel stimulatory factor for mast cells and their progenitors. J Exp Med 173: 507-510.
39. Matsuda H, Kannan Y, Ushio H, Kiso Y, Kanemoto T (1991) Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells. Exp Med 174: 7-14.
40. Rottem M, Barbieri S, Kinet JP, Metcalfe DD (1992) Kinetics of the appearance of Fc epsilon RI-bearing cell in interleukin-3-dependent mouse bone marrow cultures: correlation with histamine content and mast cell maturation. Blood 79: 972-980.
41. Thompson HL, Metcalfe DD, Kinet JP (1990a) Early expression of high-affinity receptor for immunoglobulin E (Fc epsilon RI) during differentiation of mouse mast cells and human basophils. J Clin Invest 85: 1227-1233.
42. Li Z, Liu S, Xu J (2018) Adult connective tissue-resident mast cells originate from late erythro-myeloid progenitors. Immunity 49(4): 640-653.
43. Gentek R, Ghigo C, Hoeffel G, Maxime Jacques Bulle, Rasha Msallam, et al. (2018) Hemogenic Endothelial fate mapping reveals dual developmental origin of mast cells. Immunity 48(6): 1160-1171.
44. Nilsson G, Dahlin JS (2019) New insights into the origin of mast cells. Allergy 74(4): 844-845.
45. Cop N, Ebo DG, Bridts CH, Elst J, Hagendorens MM, et al. (2018) Influence of IL-6, IL-33, and TNF-a on human mast cell activation: lessons from single cell analysis by flow cytometry. Cytometry B Clin Cytom 94(3): 405-411.
46. Desai A, Jung MY, Olivera A, Gilfillan AM, Prussin C, et al. (2016) IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3. J Allergy Clin Immunol 137(6): 1863-1871.e6.
47. Levi Schaffer F, Gibbs BF, Hallgren J, Pucillo C, Redegeld F, et al. (2022) Selected recent advances in understanding the role of human mast cells in health and disease. J Allergy Clin Immunol 149(6): 1833-1844.
48. Columbo M, Bochner BS, Marone G (1995) Human skin mast cells express functional beta 1 integrins that mediate adhesion to extracellular matrix proteins. J Immunol 154(11): 6058-6064.
49. Sperr WR, Agis H, Czerwenka K, Klepetko W, Kubista E, et al. (1992) Differential expression of cell surface integrins on human mast cells and human basophils. Ann Hematol 65: 10-16.
50. Thompson HL, Burbelo PD, Segui Real B, Yamada Y, Metcalfe DD, et al. (1989) Laminin promotes mast cell attachment. J Immunol 143: 2323-2327.
51. Thompson HL, Burbelo PD, Metcalfe DD (1990b) Regulation of adhesion of mouse bone marrow-derived mast cells to laminin. J Immunol 145: 3425-3431.
52. Dastych J, Metcalfe DD (1994) Stem cell factor induces mast cell adhesion to fibronectin. J Immunol 152(1): 213-219.
53. Friedman MM, Kaliner M (1985) In situ degranulation of human nasal mucosal mast cells: ultrastructural features and cell-cell associations. J Allergy Clin Immunol 76(1): 70-82.
54. Mecheri S, David B (1997) Unravelling the mast cell dilemma: culprit or victim of its generosity? Immunol Today 18: 212-215.
55. Mekori YA, Metcalfe DD (1999) Mast cell-T cell interactions. J Allergy Clin Immunol 104: 517-523.
56. Ortner MJ, Chignell CF (1981) The effect of concentration on the binding of compound 48/80 to rat mast cells: a fluorescence microscopy study. Immunopharmacology 3: 187-191.
57. Lagunoff D, Martin TW, Read G (1983) Agents that release histamine from mast cells. Annu Rev Pharmacol Toxicol 23: 331-351.
58. Oberhauser AF, Monck JR, Balch WE, Fernandez JM (1992) Exocytotic fusion is activated by Rab3a peptides. Nature 360: 270-273.
59. Alam R, Welter JB, Forsythe PA, Lett Brown MA, Grant JA (1989) Comparative effect of recombinant IL-1, -2, -3, -4, and -6, IFN-gamma, granulocyte-macrophage-colony-stimulating factor, tumor necrosis factor-alpha, and histamine-releasing factors on the secretion of histamine from basophils. J Immunol 142(10): 3431-3435.
60. Subramanian N, Bray MA (1987) Interleukin 1 releases histamine from human basophils and mast cells in vitro. J Immunol 138: 271-275.
61. White MV, Yoshimura T, Hook W, Kaliner MA, Leonard EJ (1989) Neutrophil attractant/activation protein-1 (NAP-1) causes human basophil histamine release. Immunol Lett 22: 151-154.
62. Brindley LL, Sweet JM, Goetzl EJ (1983) Stimulation of histamine release from human basophils by human platelet factor 4. J Clin Invest 72(4): 1218-1223.
63. Taylor AM, Galli SJ, Coleman JW (1995) Stem-cell factor, the kit ligand, induces direct degranulation of rat peritoneal mast cells in vitro and in vivo: Dependence of the in vitro effect on period of culture and comparisons of stem-cell factor with other mast cell-activating agents. Immunology 86: 427-433.
64. Demopoulos CA, Pinckard RN, Hanahan DJ (1979) Platelet-activating factor. Evidence for 1-0-alkyl-2-acetyl-sn-glyceryl-3phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem 254(19): 9355-9358.
65. Hugli TE, Muller-Eberhard, Hans J (1978) Anaphylatoxins: C3a and C5a. Adv Immunol 26: 1-53.
66. Burd PR, Rogers HW, Gordon JR, Martin CA, Jayaraman S, et al. (1989) Interleukin 3-dependent and - independent mast cells stimulated with IgE and antigen express multiple cytokines. J Exp Med 170(1): 245-257.
67. Brown MA, Pierce JH, Watson CJ, Falco J, Ihle JN, et al. (1987) B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell 50(5): 809-815.
68. Young JED, Liu CC, Butler G, Cohn ZA, Galli SJ, et al. (1987) Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Proc Natl Acad Sci 84: 9175-9179.
69. Gordon JR, Galli SJ (1990) Mast cells as a source of both preformed and immunologically inducible TNF- alpha /cachectin. Nature 346: 274-276.
70. Gordon JR, Galli SJ (1991) 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 174(1): 103-107.
71. Sobiepanek A, Kuryk L, Garofalo M, Kumar S, Baran J, et al. (2022) The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers. Int J Med Sci 23(2249): 1-31.
72. Arends MJ, Morris RG, Wyllie AH (1990) Apoptosis. The role of the endonuclease. Am J Pathol 136(3): 593-608.
73. Bianchine PJ, Burd PR, Metcalfe DD (1992) IL-3-dependent mast cells attach to plate-bound vitronectin. Demonstration of augmented proliferation in response to signals transduced via cell surface vitronectin receptors. J Immunol 149(11): 3665-3671.
74. Mekori YA, Oh CK, MetcalfeDD (1993) IL-3-dependent murine mast cells undergo apoptosis on removal of IL-3: Prevention of apoptosis by c-kit ligand. J Immunol 151: 3775-3784.
75. Horigome K, Bullock ED, Johnson E M (1994) Effects of nerve growth factor on rat peritoneal mast cells. Survival promotion and immediate-early gene induction. J Biol Chem 269(4): 2695-2702.
76. De Filippo K, Dudeck A, Hasenberg M, Nye E, Van Rooijen N, et al. (2013) Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood 121(24): 4930-4937.
77. Palomino DCT, Marti LC (2015) Chemokines and Immunity. Einstein (São Paulo)13: 469-473.
78. 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: 57-65.
79. Krystel-Whittemore M, Dileepan KN, Wood JG (2016) Mast Cell: A Multi- Functional Master Cell. Front Immunol 6: 620.