A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens.
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Mast cells were first described by Paul Ehrlich in his 1878 doctoral thesis on the basis of their unique staining characteristics and large granules. These granules also led him to the mistaken belief that they existed to nourish the surrounding tissue, and he named them "mastzellen," a German term, meaning "feeding-cells." Nowadays, they are considered part of the immune system. Mast cells are very similar to basophil granulocytes (a class of white blood cells) in blood; the similarities between mast cells and basophils has led many to speculate that mast cells are basophils that have "homed in" on tissues. However, current evidence suggests that they are generated by different precursor cells in the bone marrow. Nevertheless, both mast cells and basophils are thought to originate from bone marrow precursors expressing the CD34 molecule. The basophil leaves the bone marrow already mature while the mast cell circulates in an immature form, only maturing once in a tissue site. The tissue site an immature mast cell chooses to settle in probably determines its precise characteristics.
Two types of mast cells are recognized, those from connective tissue and a distinct set of mucosal mast cells. The activities of the latter are dependent on T-cells.
Mast cells are present in most tissues in the vicinity of blood vessels, and are especially prominent near the boundaries between the outside world and the internal milieu, such as the skin, mucosa of the lungs and digestive tract, as well as in the mouth, conjunctiva and nose.
Physiology
Mast cells play a key role in the inflammatory process. When activated, a mast cell rapidly releases its characteristic granules and various hormonal mediators into the interstitium. Mast cells can be stimulated to degranulate by direct injury (e.g physical or chemical), cross-linking of IgE receptors, or by activated complement proteins.
Mast cells express a high-affinity receptor (FcεRI) for the Fc region of Immunoglobulin E (IgE), the least-abundant member of the antibodies. This receptor is of such high affinity that binding of IgE molecules is essentially irreversible. As a result, mast cells are coated with IgE. IgE is produced by B-cells (the antibody-producing cells of the immune system). IgE molecules, like all antibodies, are specific to one particular antigen.
In allergic reactions, mast cells remain inactive until an allergen binds to IgE already in association with the cell (see above). Allergens are generally proteins or polysaccharides. The allergen binds to the Fab part of the IgE molecules on the mast cell surface. It appears that binding of two or more IgE molecules (this is called crosslinking) is required to activate the mast cell; the steric changes lead to a slight disturbance to the cell membrane structure, causing a complex sequence of reactions inside the cell that lead to its activation. Although this reaction is most well understood in terms of allergy, it appears to have evolved as a defense system against intestinal worm infestations (tapeworms, etc).
The molecules thus released into the intercellular environment include:
- preformed mediators (from the granules):
- histamine (2-5 pg/cell)
- proteoglycans, mainly heparin (active as anticoagulant)
- serine proteases
- newly formed lipid mediators (eicosanoids):
- prostaglandin D2
- leukotriene C4
- cytokines
Histamine dilates post capillary venules, activates the endothelium, and increases blood vessel permeability. This leads to local edema (swelling), warmth, redness, and the attraction of other inflammatory cells to the site of release. It also irritates nerve endings (leading to itching or pain). Cutaneous signs of histamine release are the "flare and wheal"-reaction. The bump and redness immediately following a mosquito bite are a good example of this reaction, which occurs seconds after challenge of the mast cell by an allergen.
The other physiologic activities of mast cells are much less well-understood. Several lines of evidence suggest that mast cells may have a fairly fundamental role in innate immunity -- they are capable of elaborating a vast array of important cytokines and other inflammatory mediators, they express multiple "pattern recognition receptors" thought to be involved in recognizing broad classes of pathogens, and mice without mast cells seem to be much more susceptible to a variety of infections.
