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What Are Mast Cells?

Mast cells are present in almost all vascularized tissues and act as both immune effectors and housekeeping cells. They were first described by Paul Ehrlich in 1878 and were initially thought to be a source of nourishment for surrounding tissues. Their name derives from the German “mast” meaning fattening. The source of this misconception lay in the staining of the cells with alkaline aniline dyes. These dyes enabled visualization of the large granules that their cytoplasm is full of and that characterize mast cells. Despite Ehrlich’s work, the function of mast cells remained elusive until the 1950s when a number of studies culminated in the identification of mast cells as the major repository for histamine.

Origins of Mast Cells

Like other hematopoietic cells, mast cells ultimately derive from pluripotent stem cells. Two general branches of development emerge from the stem cells, one myeloid and one lymphoid. Precisely which branch gives rise to mast cell remains to be definitively determined although a good deal of evidence from mouse studies suggests that mast cells derive from the same source as granulocyte monocyte precursors (Arinobu et al. 2005). This development is driven by the complex interplay of the PU.1 (Walsh et al. 2002), STAT5 (Shelburne et al. 2003), C/EBPalpha (Arinubo et al. 2005), MITF (Qi et al. 2013), and GATA2 (Iwasaki et al. 2006) transcription factors. The final step of the maturation of mast cells takes place in peripheral tissues where mast cell progenitors (MCPs) reside. MCPs characteristically express C-KIT/CD117 (SCF receptor) and the high affinity IgE receptor FC epsilon receptor (FcεRI).

Mast Cells and the Immune Response

Mature mast cells have a long half-life and continue to survive after fulfilling their main purpose of degranulation. Degranulation occurs when an antigen binds to the IgE/FcεRI complex present on the surface of mast cells. IgE is produced by B cells following release of IL-4 and IL-13. FcεRI has extremely high affinity for IgE such that it makes binding irreversible. Upon binding of the antigen to the IgE/FcεRI complex, activation of the Syk tyrosine kinase occurs. This sparks a signaling cascade involving phospholipase C, and increases in intracellular calcium and protein kinase C. Ultimately it is the cells exocytotic machinery, the soluble N-ethylmaleimide sensitive fusion attachment protein receptor (SNAREs) that mediates the actual release of the contents of mast cells' granules. This content includes serine proteases, histamine, serotonin, heparin, eicosanoids, and cytokines (Holowka and Baird 2015). This release leads to increased endothelial permeability in blood vessels, depolarization of nerve endings, and attraction of other immune cells to the site of release (Castells 2006).

Mast cells play a central role in inflammatory and allergic reactions with the release of histamine, central to allergic diseases such as asthma, eczema, and the life threatening anaphylaxis. Outside of this role as effectors of allergy, mast cells have been implicated in both innate and adaptive immune defenses, immune tolerance, responses to parasitic infection, and autoimmune disease (Beaven 2009).

Mast cells are found in the skin and all mucosal tissues, enabling them to act as first responders to pathogen infection. They express both Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain like receptors (NLRs), that allow them to detect and identify both bacterial and viral products. Once activated, they can recruit other immune cells such as dendritic cells, neutrophils, T cells, and B cells to the site of an injury or infection (Moon et al. 2010). There is also evidence that mast cells can act as antigen presenting cells and sit at the interface between innate and adaptive immunity. They express MHC class I, and when stimulated with IFN-γ, TNF or lipopolysaccharide, upregulate expression of MHC class II (Moon et al. 2010).

Mast Cells in Cancer, Disease, and Wound Healing

Evidence suggests that mast cells may be both pro- and anti-tumorigenic depending on the type of cancer and disease progression (Derakhshani et al. 2019). While mast cell activation is associated with the recruitment of immune cells that can inhibit tumor progression, in some cancers, like prostate cancer, mast cells may also aid tumor growth (Ma et al. 2018). This occurs through the secretion of growth factors that promote angiogenesis, like VEGF, and FGF-2. Tumor derived peptides may also recruit and activate mast cells in the tumor, further promoting tumor growth (Rao and Brown 2008). Mast cells have therefore been proposed as a target for cancer therapy for certain cancer types (Derakhshani et al. 2019).

Mast cells are important players in inflammatory associated diseases like inflammatory bowel disease, psoriasis, and multiple sclerosis (González-de-Olano and Álvarez-Twose  2018). In multiple sclerosis, they have been found within demyelinated lesions, with histamine released by mast cells facilitating autoreactive T cells entry into the central nervous system and disease progression (Komi et al. 2020).

Additionally, mast cells participate in wound healing, including the initial inflammation and repair of the damaged tissue. Mast cells are activated in response to an injury and produce VEGF, NGF, FGF-2, and PDGF, as well as histamine and tryptase to facilitate wound repair (Rao and Brown 2008).

Read our blog “A MASTer Immune Cell” to learn more about the roles of mast cells outside of allergy.

Mast Cell Markers

To view antibodies available to these markers simply click on the marker.

References

• Arinobu Y et al. (2005). Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. Proc Natl Acad Sci U S A. 102, 18105-18110.
• Beaven MA. (2009). Our perception of the mast cell from Paul Ehrlich to now. Eur J Immunol. 39, 11-25.
• Castells M. (2006). Mast cell mediators in allergic inflammation and mastocytosis. Immunol Allergy Clin North Am. 26, 465-485.
• Derakhashani A et al. (2019). Mast cells: a double-edged sword in cancer. Immunol Lett 209, 28-35.
• González-de-Olano D and Álvarez-Twose I (2018). Mast cells as key players in allergy and inflammation. J Investig Allergol Clin Immunol 28, 365-378.
• Holowka D, Baird B. (2015). Nanodomains in early and later phases of Fc?RI signalling. Essays Biochem. 57, 147-163.
• Iwasaki H et al. (2006). The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev. 20, 3010-3021.
• Komi DEA et al. (2020). Mast cell biology at molecular level: a comprehensive review. Clin Rev Allergy Immunol 58, 342-365.
• Ma Z et al. (2018). The effect of mast cells on the biological characteristics of prostate cancer cells. Cent Eur J Immunol 43, 1-8.
• Moon TC et al. (2010). Advances in mast cell biology: new understanding of heterogeneity and function.  Mucosal Immunol 3, 111-128.
• Rao KN and Brown MA (2008). Mast cells: multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci 1143, 83-104.
• Shelburne CP et al. (2003). Stat5 expression is critical for mast cell development and survival. Blood. 102, 1290-1297.
• Qi X et al. (2013). Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates. Immunity. 39, 97-110.
• Walsh JC et al. (2002). Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates. Immunity. 17,665-676.

Further Reading

• Dahlin JS and Hallgren J. (2015). Mast cell progenitors: origin, development and migration to tissues. Mol Immunol. 63, 9-17.