Mast Cells

Abstract

Mast cell is a type of connective tissue cell but originates from the haematopoietic stem cell. Adult mouse mast cell‐committed progenitor, which is the common myeloid progenitor lineage, can be identified in bone marrow. Additionally, a unique progenitor having bipotent activity (e.g. basophil/mast cell progenitor) is found in the spleen, which is unique lymphoid organ having a function to sustain hematopoiesis. Mast cell‐lineage specification is coordinated by transcription factor GATA‐binding protein‐1 (GATA‐1), GATA‐2, PU.1 and CCAAT/enhancer‐binding protein‐α, and its maturation process is regulated by microphthalmia transcription factor. Mast cell progenitors distribute in various tissues through the blood stream by using known/unknown chemokines and integrins and located around blood vessels, peripheral nerves or lymphatic vessels. The most established function of mast cells is amplification of immunoglobulin E‐dependent hypersensitivity reaction. Mouse models have mainly been utilised to understand the mast cell biology and have given us many evidences especially in the developmental origin of mast cell. Although controversial results have emerged in the role of mast cells, recent advances in next generation mast cell‐deficient mice models will improve the knowledge about the roles of mast cell in various disease settings.

Key Concepts:

  • Adult mouse mast cell progenitors (MCPs), which differentiate through the stage of common myeloid progenitor, are able to detect by combination of specific cell surface markers.

  • Adult mouse MCPs are identifiable in bone marrow. Bipotent basophil/mast cell progenitors (BMCPs) can be found in the spleen. The developmental and functional relationship of these cells remains to be determined.

  • Mouse mast cells are classified into two types (mucosal and connective tissue type) by histological sites (e.g. mucosa or connective tissue). However, human mast cells are classified into two types by its protease expression pattern (e.g. tryptase+ chymase type and tryptase+ chymase+ type). Recently, nonclassical protease expression patterns have been found in human and mouse mast cells.

  • Mast cell heterogeneity is determined by tissue microenvironments.

  • Although KIT mutant mice have long been used for the study of mast cell function, some subsidiary effects are concerned because KIT mutant mice have several defects other than mast cells. Recently developed genetically engineered mast cell deficient mice may give us more convincing evidences of mast cell function in various diseases except for the established function of IgE‐mast cell in immediate hypersensitivity.

Keywords: basophil; IgE; immediate hypersensitivity; KIT ligand; KIT receptor tyrosine kinase; mast cell; MITF

Figure 1.

Development of mast cells from the multipotential haematopoietic stem cell. The presence of bipotent progenitor committed to basophil and mast cell (BMCP) has been shown in the spleen of mice (Arinobu et al., ). BaP, basophil progenitor; Bas, basophil; BMCP, basophil/mast cell progenitor; CMP, common myeloid progenitor; DC, dendritic cell; E, erythrocyte; EoP, eosinophil progenitor; Eos, eosinophil; ETP, earliest thymic progenitor; ILC, innate lymphoid cell (e.g. NK cell, natural helper cell etc.); LMPP, lymphoid‐primed multipotent progenitor; MC, mast cell; MCP, mast cell‐committed progenitor; MEP, megakaryocyte/erythrocyte progenitor; MHSC, multipotential haematopoietic stem cell; Mono, monocyte; Neu, neutrophil; NMoP, neutrophil/monocyte progenitor; PL, platelet; proB, B cell progenitor.

Figure 2.

Differentiation of connective tissue‐type mast cells (CTMCs) and mucosal‐type mast cells (MMCs), and molecular mechanisms of mast cell progenitor settlement to anatomical sites. (a) Mast cells differentiate into CTMCs or MMCs dependently of tissue microenvironmental factors. (b) Mast cell progenitors are recruited during homeostatic/inflammatory condition. Distinct/overlapping molecules on MCPs/stroma are critical for tissue recruitment of MCPs in mice. Bas, basophil; BMCP, basophil/mast cell progenitor; CMP, common myeloid progenitor; CTMC, connective tissue‐type mast cell; MCP, mast cell‐committed progenitor; MHSC, multipotential haematopoietic stem cell; MMC, mucosal mast cell.

Figure 3.

Transcription factors that are involved in the development of mast cells. GATA‐1, GATA‐2 and PU.1 are required in the early stage; C/EBPα in the intermediate stage and MITF in the late stage. BMCP, basophil/mast cell progenitor; CMP, common myeloid progenitor.

Figure 4.

Human mast cell subtype proportions in various anatomical sites. MCtc, tryptase‐positive, chymase‐positive mast cell; MCt, tryptase‐positive, chymase‐negative mast cell.

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Further Reading

Galli SJ and Tsai M (2012) IgE and mast cells in allergic disease. Nature Medicine 18: 693–704.

Gilfillan AM and Metcalfe DD (eds) (2011) Mast cell biology: Contemporary and Emerging Topics. Advances in Experimental Medicine and Biology, vol. 716, pp. 143–159. Austin, USA: Landes Bioscience and Springer.

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How to Cite close
Oboki, Keisuke, Hagiyama, Man, Inoue, Takao, and Ito, Akihiko(Jan 2013) Mast Cells. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001203.pub3]