Mast cell
A mast cell (or mastocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. It plays a role in allergy and wound healing.
Classification
Mast cells derive their name from the obsolete theory that its characteristic granula contain nutrients for other tissues. 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 choses to settle in probably determines its precise characteristics.
Two types of mast cells are recognised, 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 the skin, mucosa of the lungs and digestive tract, as well as in the mouth and nose.
Physiology
Mast cells express a high-affinity receptor (FcεRI) for Immunoglobulin E (IgE), the least abundant member of the antibodies. IgE is, in turn, synthetised by B-cells (the antibody-producing cells of the immune system). IgE molecules, like all antibodies, are specific for one specific epitope.
Mast cells remain inactive until an allergen binds to the cell. Allergens are generally proteins or polysaccharides. The allergen binds to the Fc part of the IgE molecules coated on the mast cell surface. It appears that binding to two IgE molecules 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 activation of the cell.
When activated, a mast cell rapidly releases its characteristic granules and various hormonal mediators into the interstitium. Other forms of activation besides IgE (such as by the complement system) have been described.
The molecules thus released into the intercellular environment include:
Histamine leads to the contraction of smooth muscle cells, activates endothelium and irritates nerve endings (leading to itching or pain). Cuteanous signs of histamine release are the "flare and wheal"-reaction. This occurs seconds after challenge of the mast cell by an allergen.
Role in disease
Allergic disease
Many forms of cutaneous and mucosal allergy are mediated for a large part by mast cells; they play a central role in asthma, eczema, itch (from various causes) and allergic rhinitis and allergic conjunctivitis. Antihistamine drugs act by blocking the action of histamine on nerve endings. Cromoglycate-based drugs (sodium cromoglycate, nedocromil) block a calcium channel essential for mast cell degranulation, stabilising the cell and preventing release of histamine and related mediators. Leukotriene antagonists (such as montelukast and zafirlukast) block the action of leukotriene mediators, and are being used increasingly in allergic diseases.
Anaphylaxis
In anaphylaxis (a severe systemic reaction to allergens, such as nuts, bee stings or drugs), body-wide degranulation of mast cells leads to vasodilatation and, if severe, symptoms of life-threatening shock.
Mast cell tumors
Mastocytosis is a rare condition featuring proliferation of mast cells. It exists in a cutaneous and systemic form, with the former being limited to the skin and the latter involving multiple organs.
Sources
- Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2003;111(2 Suppl):S486-94. PMID .
