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| Melanocyte | |
|---|---|
 Melanocyte andmelanin | |
| Details | |
| Pronunciation | /məˈlænəˌsaɪt,-noʊ-/ ⓘ or/ˈmɛlənəˌsaɪt,-noʊ-/[1][2] |
| Precursor | Neural crest |
| Location | Skin |
| Function | Melanin production |
| Identifiers | |
| Latin | melanocytus |
| MeSH | D008544 |
| TH | H2.00.03.0.01016 |
| FMA | 70545 |
| Anatomical terms of microanatomy | |
Melanocytes aremelanin-producingneural crest-derived[3]cells located in the bottom layer (thestratum basale) of the skin'sepidermis, the middle layer of theeye (theuvea),[4] theinner ear,[5]vaginal epithelium,[6]meninges,[7]bones,[8] andheart found in manymammals andbirds.[9] Melanin is a darkpigment primarily responsible forskin color. Once synthesized, melanin is contained in specialorganelles calledmelanosomes which can be transported to nearbykeratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection againstUV radiation. Melanocytes also have a role in theimmune system.
Through a process called melanogenesis, melanocytes producemelanin, which is a pigment found in theskin,eyes,hair,nasal cavity, andinner ear. This melanogenesis leads to a long-lasting pigmentation, which is in contrast to the pigmentation that originates from oxidation of already-existing melanin.
There are both basal and activated levels of melanogenesis; in general, lighter-skinned people have low basal levels of melanogenesis. Exposure to UV-B radiation causes increased melanogenesis. The purpose of melanogenesis is to protect thehypodermis, the layer under the skin, from damage by UV radiation. The color of the melanin is black, allowing it to absorb a majority of the UV light and block it from passing through the epidermis.[10]
Since the action spectrum ofsunburn and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism.[11] The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation ofcyclobutane pyrimidine dimers (CPDs) -direct DNA damage.
Typically, between 1000 and 2000 melanocytes are found per square millimeter of skin or approximately 5% to 10% of the cells in the basal layer of epidermis. Although their size can vary, melanocytes are typically 7 μm in length.[citation needed]
Both lightly and darkly pigmented skin contain similar numbers of melanocytes,[12] with difference inskin color due to differences the packing ofeumelanin into themelanosomes ofkeratinocytes: those in dark-toned skin are "packaged into peri-nuclear distributed, ellipsoid" melanosomes while those light-tone skin are "assembled into clustered small, circular melanosomes".[13] There are also differences in the quantity and relative amounts ofeumelanin andpheomelanin.[13] Pigmentation including tanning is under hormonal control, including theMSH and ACTH peptides that are produced from the precursor proopiomelanocortin.
Vitiligo is a skin disease where people lack melanin in certain areas in the skin.
People with oculocutaneousalbinism typically have a very low level of melanin production. Albinism is often but not always related to theTYR gene coding thetyrosinase enzyme. Tyrosinase is required for melanocytes to produce melanin from theamino acidtyrosine.[14] Albinism may be caused by a number of other genes as well, likeOCA2,[15]SLC45A2,[16]TYRP1,[17] andHPS1[18] to name some. In all, already 17 types of oculocutaneous albinism have been recognized.[19] Each gene is related to different protein having a role in pigment production.
People withChédiak–Higashi syndrome have a buildup of melanin granules due to abnormal function ofmicrotubules.
In addition to their role as UV radical scavengers, melanocytes are also part of the immune system, and are considered to be immune cells.[20] Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics withdendritic cells: branched morphology;phagocytic capabilities; presentation ofantigens toT-cells; and production and release ofcytokines.[20][21][22] Although melanocytes are dendritic in form and share many characteristics with dendritic cells, they derive from different cell lineages. Dendritic cells are derived fromhematopoietic stem cells in thebone marrow. Melanocytes on the other hand originate fromneural crest cells. As such, although morphologically and functionally similar, melanocytes and dendritic cells are not the same.
Melanocytes are capable of expressingMHC Class II,[21] a type of MHC expressed only by certain antigen presenting cells of the immune system, when stimulated by interactions with antigen or cytokines. All cells in any given vertebrate express MHC, but most cells only expressMHC class I. The other class of MHC,Class II, is found only on "professional" antigen presenting cells such as dendritic cells,macrophages,B cells, and melanocytes. Importantly, melanocytes stimulated by cytokines express surface proteins such asCD40 andICAM1 in addition to MHC class II, allowing for co-stimulation of T cells.[20]
In addition to presenting antigen, one of the roles of melanocytes in the immune response is cytokine production.[23] Melanocytes express many proinflammatory cytokines includingIL-1,IL-3,IL-6,IL-8,TNF-α, andTGF-β.[20][21] Like other immune cells, melanocytes secrete these cytokines in response to activation ofPattern Recognition Receptors (PRRs) such asToll Like Receptor 4 (TLR4) which recognizeMAMPs. MAMPs, also known as PAMPs, are microbial associated molecular patterns, small molecular elements such as proteins, carbohydrates, and lipids present on or in a given pathogen. In addition, cytokine production by melanocytes can be triggered by cytokines secreted by other nearby immune cells.[20]
Melanocytes are ideally positioned in theepidermis to be sentinels against harmful pathogens. They reside in thestratum basale,[23] the lowest layer of theepidermis, but they use their dendrites to interact with cells in other layers,[24] and to capture pathogens that enter the epidermis.[21] They likely work in concert with bothkeratinocytes andLangerhans cells,[20][21] both of which are also activelyphagocytic,[23] to contribute to the immune response.
Tyrosine is the non-essential amino acid precursor of melanin. Tyrosine is converted to dihydroxyphenylalanine (DOPA) via the enzyme tyrosinase. Then DOPA is polymerized into melanin. The copper-ion based enzyme-catalyzed oxidative transformation of catechol derivative dopa to light absorbingdopaquinone toindole-5,6-quinone is clearly seen following the polymerization to melanin, the color of the pigment ranges from red to dark brown.
Numerous stimuli are able to alter melanogenesis, or the production of melanin by cultured melanocytes, although the method by which it works is not fully understood. Increased melanin production is seen in conditions whereadrenocorticotropic hormone (ACTH) is elevated, such asAddison's andCushing's disease. This is mainly a consequence of alpha-MSH being secreted along with the hormone associated with reproductive tendencies in primates. Alpha-MSH is a cleavage product of ACTH that has an equal affinity for the MC1 receptor on melanocytes as ACTH.[25]
Melanosomes arevesicles that package the chemical inside aplasma membrane. Themelanosomes are organized as a cap protecting the nucleus of thekeratinocyte. When ultraviolet rays penetrate the skin and damage DNA,thymidine dinucleotide (pTpT) fragments from damagedDNA will trigger melanogenesis[26] and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.
Theprecursor of the melanocyte is themelanoblast. In adults, stem cells are contained in the bulge area of theouter root sheath ofhair follicles. When a hair is lost and the hair follicle regenerates, the stem cells are activated. These stem cells develop into both keratinocyte precursors and melanoblasts - and these melanoblasts supply both hair and skin (moving into thebasal layer of theepidermis). There is additionally evidence that melanocyte stem cells are present in cutaneous nerves, with nerve signals causing these cells to differentiate into melanocytes for the skin.[27]
