melanocyte
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Melanocytes are
melanin Melanin (; from el, μέλας ''melas'', "black, dark") is a broad term for a group of natural pigments found in most organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individu ...

melanin
-producing
neural crest Neural crest cells are a temporary group of cells unique to vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdo ...
-derived
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a room used to hold peopl ...
located in the bottom layer (the
stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis The epidermis is the outermost of the three layers that make up the skin, the inner layers being the ...
) of the skin's
epidermis The epidermis is the outermost of the three layers that comprise the skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Oth ...
, the middle layer of the
eye Eyes are organs of the visual system The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which ...

eye
(the
uvea The uvea (; Lat. ''uva'', "grape"), also called the ''uveal layer'', ''uveal coat'', ''uveal tract'', ''vascular tunic'' or ''vascular layer'' is the pigmented middle of the three concentric layers that make up an eye Eyes are organs of t ...
), the
inner ear Inner Ear (established in 2007 in Bodø, Norway) is a Norwegian record label initiated and led by the brothers and jazz musicians Tore Johansen and Roger Johansen (musician), Roger Johansen. They opened Inner Ear to release their music when their ...

inner ear
,
vaginal epithelium In mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), and characterized by the presence of mammary glands which in Female#Mammalian female, femal ...
, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against Ultraviolet, UV radiation. Melanocytes also have a role in the immune system.


Function

Through a process called melanogenesis, melanocytes produce
melanin Melanin (; from el, μέλας ''melas'', "black, dark") is a broad term for a group of natural pigments found in most organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individu ...

melanin
, which is a pigment found in the human skin, skin,
eye Eyes are organs of the visual system The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which ...

eye
s, hair, nasal cavity, and
inner ear Inner Ear (established in 2007 in Bodø, Norway) is a Norwegian record label initiated and led by the brothers and jazz musicians Tore Johansen and Roger Johansen (musician), Roger Johansen. They opened Inner Ear to release their music when their ...

inner 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 the Subcutaneous tissue, hypodermis, 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. Since the action spectrum of sunburn and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism. The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of cyclobutane 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. The difference in Human skin color, skin color between lightly and darkly pigmented individuals is due not to the number (quantity) of melanocytes in their skin, but to the melanocytes' level of activity (quantity and relative amounts of eumelanin and pheomelanin). This process is under hormonal control, including the Melanocyte-stimulating hormone, MSH and ACTH peptides that are produced from the precursor proopiomelanocortin. Vitiligo is a skin disease where people suffer from melanin lack in certain areas in the skin. People with oculocutaneous albinism typically have a very low level of melanin production. Albinism is often but not always related to the ''TYR'' gene coding the tyrosinase enzyme. Tyrosinase is required for melanocytes to produce melanin from the amino acid tyrosine. Albinism may be caused by a number of other genes as well, like ''OCA2'', ''SLC45A2'', ''TYRP1'', and ''HPS1'' to name some. In all, already 17 types of oculocutaneous albinism have been recognized. Each gene is related to different protein having a role in pigment production. People with Chédiak–Higashi syndrome have a buildup of melanin granules due to abnormal function of microtubules.


Role in the immune system

In addition to their role as UV radical scavengers, melanocytes are also part of the immune system, and are considered to be immune cells. Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics with dendritic cells: branched morphology; Phagocytosis, phagocytic capabilities; presentation of antigens to T cell, T-cells; and production and release of cytokines. Although melanocytes are dendritic in form and share many characteristics with dendritic cells, they are derived from two different cell lineages. Dendritic cells are derived from hematopoietic stem cells in the bone marrow. Melanocytes on the other hand originate from Neural crest, neural crest cells. As such, although morphologically and functionally similar, melanocytes and dendritic cells are not the same. Melanocytes are capable of expressing MHC class II, MHC Class II, 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 express MHC class I. The other class of MHC, MHC class II, 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 as CD40 (protein), CD40 and ICAM-1, ICAM1 in addition to MHC class II, allowing for co-stimulation of T cells. In addition to presenting antigen, one of the roles of melanocytes in the immune response is cytokine production. Melanocytes express many proinflammatory cytokines including Interleukin-1 family, IL-1, Interleukin 3, IL-3, Interleukin 6, IL-6, Interleukin 8, IL-8, Tumor necrosis factor alpha, TNF-α, and Transforming growth factor beta, TGF-β. Like other immune cells, melanocytes secrete these cytokines in response to activation of Pattern recognition receptor, Pattern Recognition Receptors (PRRs) such as TLR4, Toll Like Receptor 4 (TLR4) which recognize Pathogen-associated molecular pattern, MAMPs. 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. Melanocytes are ideally positioned in the epidermis to be sentinels against harmful pathogens. Melanocytes reside in the
stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis The epidermis is the outermost of the three layers that make up the skin, the inner layers being the ...
, the lowest layer of the epidermis, but they use their dendrites to interact with cells in other layers, and to capture pathogens that enter the epidermis. Melanocytes likely work in concert with both keratinocytes and Langerhans cells, both of which are also actively Phagocytosis, phagocytic, to contribute to the immune response.


Melanogenesis

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 absorbing dopaquinone to indole-5,6-qionone is clearly seen following the polymerization to melanin, the color of the pigment ranges from red to dark brown.


Stimulation

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. Certain melanocortins have been shown in laboratory testing to have effect on appetite and sexual activity in mice. Eicosanoids, retinoids, oestrogens, melanocyte-stimulating hormone, endothelins, psoralens, hydantoin, forskolin, cholera toxin, isobutylmethylxanthine, diglyceride, diacylglycerol analogues, and UV irradiation all trigger melanogenesis and, in turn, pigmentation. Increased melanin production is seen in conditions where Adrenocorticotropic Hormone, adrenocorticotropic hormone (ACTH) is elevated, such as Addison's disease, Addison's and Cushing'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. Melanosomes are Vesicle (biology), vesicles that package the chemical inside a plasma membrane. The melanosomes are organized as a cap protecting the nucleus of the keratinocyte. When ultraviolet rays penetrate the skin and damage DNA, thymidine dinucleotide (pTpT) fragments from damaged DNA will trigger melanogenesis and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.


Stem cells

The Precursor cell, precursor of the melanocyte is the melanoblast. In adults, stem cells are contained in the bulge area of the outer root sheath of hair 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 the Stratum basale, basal layer of the epidermis). 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.


Clinical significance

* Melanoma - Cancer affecting melanocytes * Melanocytic tumors *Melanocytic tumors of uncertain malignant potential *Vitiligo - Decreased number of melanocytes due to autoimmune destruction causing decreased melanin *Albinism - Normal number of melanocytes, but decreased melanin production due to decreased tyrosinase activity or defective tyrosine transport *Melasma (Chloasma) - Patchy hyperpigmentation of the skin Normal number of melanocytes with increased melanin production causing hyperpigmentation. Associated with pregnancy or oral contraceptive pill use. *Addison's disease, Addison disease *Nevus depigmentosus


See also

* Chromatophore (the pigment cell type found in poikilotherm animals) * Eye color *Mole (skin marking) * Tanning activator *List of human cell types derived from the germ layers


References


Further reading

* *


External links

* - "Eye: fovea, RPE" * - "Integument: pigmented skin" {{Authority control Human cells Pigment cells Skin anatomy Epithelial cells