- 1 Mast Cell
- 1.1 Introduction
- 1.2 History
- 1.3 Physiology
- 1.4 Pathology
- 1.5 Glossary
multifunctional purpose (don't have to go into too much detail -> more depth in following sections
Origin and Differentiation
(references to be added)
Mast cells have a hematopoietic origin from the bone marrow. This was shown when a patient suffering from acute myeloid leukaemia underwent an allogeneic bone marrow transplant and after 198 days post transplant mast cells were found. The researchers used Polymerase chain reaction to show that the mast cells showed donor’s genotype.
A mast cell committed precursor has been found in mice by using mast cell specific antibodies to separate them out immunomagnetically. These precursors had mRNA present for some subunits of FCeR1, but did not express the receptor on their surface. They also had mRNA for mast cell specific proteases.
As stated above research suggests in adults mast cells are produced from haematopoietic origins by a committed precursor. However in rat embryos, using similar immunological methods, it has been shown that embryos mature in aorta-gonad-meso-nephros region (AGM) which indicates that in human embryos mast cells may develop outside of the bone marrow
Interestingly mast cells do not differentiate in the bone marrow, their precursor cells travel to extramedullary sites with good vasculature such as connective region of the skin or mucosa of the GIT. (draw image of this process).
The migration of mast cell precursors is tissue specific. It depends on the interaction of the MCP's integrins binding to the corrsponding adhesion molecules in the mucosa called MAdCAM-1. (gurish et al 2001, pg 701 D.S.). The precursors also express chemokine receptors that may play a role in migration (abonia et al., 2005)
There are both intrinsic and extrinsic factors required for Mast cell differentiation. The following have been discovered as a result of mice carrying genetic mutations:
|Fibroblast derived Growth factors on haematopoietic stem cells . There are also growth factors that inhibit mastopoesis such as thrombopoetin, which acts by down-regulating GATA1||Transcription factor MitF - Involved in c-kit expression that influences mast cell specific protease expression|
|IL-3 from T cells5 - Induced from T cells as a result of external stimuli. For example parasite infections. It has been shown to be responsible for Mast Cell survival, developement and maturation in vitro (Metcalf, 1986)703D.S.||Transcription factors: Gata1 and Gata 1 - Expressed throughout differentiation in vitro. Mutation in GATA1 gene affects all stages of differentiation of mast cells|
This is different to activation in that it's how the biogenesis of the mediators occurs, not how an antigen triggers the degranulation. pg 4 moon et al
706, de silva
<pubmed>25062998</pubmed> <pubmed>25452755</pubmed> <pubmed>12592295</pubmed>
<pubmed>22561833</pubmed> review on igE interactions: http://www.nature.com/nm/journal/v18/n5/full/nm.2755.html
<pubmed>21333342</pubmed> autophagy: http://www.sciencedirect.com/science/article/pii/S0091674910030381
Mast cells are sentinel cells that are found distributed within the connective tissue throughout the body and play an important role in both acute and chronic inflammation. Mast cells that are coated with IgE antibodies specific for certain environmental antigens are triggered to release histamine and other cytokines that induce early vascular changes that are hallmarks of acute inflammation.  The immediate responsibility of mast cells is to recognise that infection by a pathogen has occurred, which is achieved by direct recognition of the pathogen by pattern recognition receptors that are activated in response to pathogen-associated molecular patterns (PAMPs).  A study conducted by Supajatura et al. demonstrated that the activation of different toll-like receptors (TLR2 or TLR4) by varying PAMPs resulted in differential activation of mast cells evident in lypopolysaccharide stimulation of TLR4 resulting in cytokine release compared to peptidoglycan stimulation of TLR2 receptors resulting in both degranulation and cytokine production. However, mast cells can act directly on pathogens through the production of reactive oxygen species and phagocytosis, as demonstrated by the engulfing of Fim-H expressing enterobacteria. 
Mast cells also play a major role in atopic diseases such as asthma, eczema, anaphylaxis and allergic rhinitis. The basis of these allergic diseases is the activation and binding of the high-affinity immunoglobulin E (IgE) receptor FceR1 to initiate receptor clustering and release of mediators, a signalling network dependent on the strength and type of stimulus.  Furthermore, similarly to neutrophils, mast cells have been seen to produce extracellular traps through the utilisation of the cathelicidin LL-37, histones and tryptase.  These three products of mast cells form the structural foundation of the extracellular traps, demonstrated to trap the bacteria S. pyogenes when in close proximity in co-culture in vitro. 
Role of mast cells in parathyroid bone disease
An increased number of mast cells in the bone marrow can be linked with parathyroid bone disease, most common of which being chronic hyperparathyroidism (HPT). Those suffering from HPT have a disturbed immune function, and mast cells play a major role in innate immunity. Parathyroid hormone (PTH) significantly increases the number of mast cells in those with HPT. There is a 5-fold increase in bone marrow mast cells in those with HPT as compared to the controls. Elevated levels of PTH increase migration of preoestoblastic fibroblasts to the bone surface, and while these generally differentiate into osteoblasts, the increased PTH levels cause terminal differentiation to be impaired. The accumulation of mast cells on bone surfaces as a response to elevated PTH levels lead to this PTH-induced peritrabcular fibrosis, and cause the excessive recruitment of fibroblasts on bone surfaces. An increase in kit- ligand expression causes the build up of mast cells, as it is a potent chemotactic factor for these mast cells. Combined with an increased PDFG-A gene expression, these peritrabcular mast cells promote fibrosis, ultimately leading to bone disease.
Role of mast cells in eczema
Atopy is a common syndrome underlying eczema is characterised by high Immunoglobulin E (IgE) responsiveness. IgE is produced in response to common antigens, and is bound to the surface of mast cells, which play an essential role in atopic conditions such as eczema. Mast cell chymase (MCC) in particular is involved in this condition, and is a serine protease which accumulates in the dermis of the skin. An increase in MCC promotes skin inflammation and conditions such as eczema. The polymorphism of MCC is significantly associated with the occurrence of eczema, and different variations of this MCC is one source of genetic risk for the condition.
Atopy Allergic Rhinitis: commonly known as hay fever Immunoglobulin E:antibodies produced by the body's immune system
FceR1: high affinity Immunoglobulin E receptor
- Robins Basic Pathology Kumar, Vanay; Abbas, Abul K.; Aster, Jon C., Philadelphia: Elsevier Saunders., 2013