Mast cell 254062 226012604 2008-07-16T13:03:51Z 89.172.234.144 /* Physiology */ [[Image:SMCpolyhydroxysmall.jpg|thumb|300px|Mast cells]] A '''mast cell''' (or ''mastocyte'') is a resident [[cell (biology)|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 [[pathogen]]s.<ref name=Prussin>{{cite journal |author=Prussin C, Metcalfe DD |title=IgE, mast cells, basophils, and eosinophils |journal=J Allergy Clin Immunol |volume=111 |issue=2 Suppl |pages=S486–94 |year=2003 |pmid=12592295|doi=10.1067/mai.2003.120}}</ref> ==Origin and classification== [[Image:Mast cell.png|thumb|Mast cell]] 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" (from Greek ''masto'', to feed)<ref>Ehrlich P. ''Beiträge zur Theorie und Praxis der histologischen Färbung.'' Dissertation at Leipzig University, 1878.</ref> They are now considered to be part of the [[immune system]]. Mast cells are very similar to [[basophil granulocyte]]s (a class of [[white blood cell]]s) 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.<ref name=Prussin/> Two types of mast cells are recognized, those from [[connective tissue]] and a distinct set of [[mucosa]]l mast cells. The activities of the latter are dependent on [[T-cell]]s.<ref>{{cite book |title=Allergy and Allergic Diseases: The New Mechanisms and Therapeutics |last=Denburg |first=Judah A. |year=1998 |publisher=Humana Press |isbn=0896034046 }}</ref> 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 [[lung]]s and [[digestive tract]], as well as in the [[mouth]], [[conjunctiva]] and [[nose]].<ref name=Prussin/> ==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 [[Degranulation|degranulate]] by direct injury (e.g physical or chemical), cross-linking of IgE receptors, or by activated complement proteins.<ref name=Prussin/> 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-cell]]s (the antibody-producing cells of the immune system). IgE molecules, like all antibodies, are specific to one particular [[antigen]].<ref name=Prussin/> [[Image:Mast cells.jpg|thumb|right|220px|The role of mast cells in the development of allergy.]] In allergic reactions, mast cells remain inactive until an [[allergen]] binds to IgE already in association with the cell (see above). Allergens are generally [[protein]]s or [[polysaccharide]]s. 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).<ref name=Prussin/> The molecules thus released into the extracellular environment include:<ref name=Prussin/> * preformed mediators (from the granules): ** [[histamine]] (2-5 [[picogram|pg]]/cell) ** proteoglycans, mainly [[heparin]] (active as [[anticoagulant]]) ** [[serine protease]]s * newly formed lipid mediators ([[eicosanoid]]s): ** [[prostaglandin D2]] ** [[leukotriene]] C4 * [[cytokine]]s 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 ending]]s (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.<ref name=Prussin/>[[Image:histamine.png|thumb|left|170px|Structure of histamine]] 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.{{Fact|date=June 2007}} Mast cell granules carry a variety of bioactive chemicals. These granules have been found to be transferred to adjacent cells of the immune system and [[neurons]] via transgranulation via their [[pseudopodia]].<ref>{{cite journal |author=Wilhelm M, Silver R, Silverman AJ |title=Central nervous system neurons acquire mast cell products via transgranulation |journal=Eur J Neurosci |volume=22 |issue=9 |pages=2238–48 |year=2005 |pmid=16262662 |doi=10.1111/j.1460-9568.2005.04429.x}}</ref> ==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. [[Cromoglicate]]-based drugs (sodium cromoglicate, nedocromil) block a calcium channel essential for mast cell degranulation, stabilizing 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.<ref name=Prussin/> ===Anaphylaxis=== In [[anaphylaxis]] (a severe systemic reaction to [[allergen]]s, such as nuts, bee stings or drugs), body-wide degranulation of mast cells leads to vasodilation and, if severe, symptoms of life-threatening [[Shock (medical)|shock]].{{Fact|date=June 2007}} ===Autoimmunity=== Mast cells are implicated in the pathology associated with the autoimmune disorders [[rheumatoid arthritis]], [[bullous pemphigoid]], and [[multiple sclerosis]]. They have been shown to be involved in the recruitment of inflammatory cells to the joints (e.g. [[rheumatoid arthritis]]) and skin (e.g. [[bullous pemphigoid]]) and this activity is dependent on antibodies and complement components. {{Fact|date=June 2007}} ===Mast cell disorders=== [[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.<ref name=Prussin/> [[Mast cell tumor]]s are often seen in dogs and cats.<ref>{{cite web | title = Cutaneous Mast Cell Tumors | work = The Merck Veterinary Manual | date = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/72231.htm | accessdate = 2007-07-08 }}</ref> ==References== {{reflist}} ==External links== * {{MeshName|Mast+cells}} {{Blood}} [[Category:Granulocytes]] [[Category:cell biology]] [[Category:Human cells]] [[ca:Mastòcit]] [[da:Mastcelle]] [[de:Mastzelle]] [[es:Mastocito]] [[fr:Mastocyte]] [[ko:비만 세포]] [[he:תא פיטום]] [[mk:Мастоцит]] [[nl:Mestcel]] [[ja:肥満細胞]] [[pl:Komórka tuczna]] [[pt:Mastócito]] [[ru:Тучные клетки]] [[sr:мастоцит]] [[fi:Syöttösolu]] [[sv:Mastcell]] [[tr:Mast hücresi]] [[zh:肥大细胞]] [[it:mastocita]]