Innate Immunity Antibodies

Mast Cells

Characterization, markers and antibodies

First described by Paul Ehrlich in 1878 mast cells were initially thought to be a source of nourishment for surrounding tissues. The source of this misconception lay in the staining of the cells with alkaline aniline dyes. This dye enabled visualization of the large granules 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.

Like other haematopoietic cells, mast cells ultimately derive from pluripotent stem cells. Two general branches of development emerge from the stem cells level 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).

Mature mast cells have a long half-life and continue to survive after fulfilling its 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 irreversibe. 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, 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 mediate the actual release of the contents of the mast cell granules. The contents of the granules include serine proteases, histamine, serotonin, heparin, eicosanoids and cytokines (Holowka and Baird 2015).

Release of the contents of mast cells granules 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). The release of histamine is central to allergic diseases such as asthma, eczema and the life threatening anaphylaxis. In addition to this inflammatory response mast cells have also been implicated in responses to parasite infection and autoimmune diseases (Beaven 2009).

A number of different markers can be used to identify mast cells:

Human Markers

Mice Markers

FcεRI

FcεRI

CD117/C-Kit

CD117/C-Kit

CD23

CD23

CD203c

CD203c


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.
  • Holowka D, Baird B. (2015). Nanodomains in early and later phases of FcɛRI 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.
  • 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.
  • Shelburne CP et al. (2003). Stat5 expression is critical for mast cell development and survival. Blood. 102, 1290-1297.
  • 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.