Melanocyte

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Melanocyte
Illu skin02.jpg
Melanocyte and melanin
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 are melanin-producing neural crest-derived [3] cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), [4] the inner ear, [5] vaginal epithelium, [6] meninges, [7] bones, [8] and heart found in many mammals and birds. [9] 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 UV radiation. Melanocytes also have a role in the immune system.

Contents

Function

Illustration of a melanocyte Blausen 0632 Melanocyte.png
Illustration of a melanocyte
Micrograph of melanocytes in the epidermis Micrograph of melanocytes in the epidermis.jpg
Micrograph of melanocytes in the epidermis

Through a process called melanogenesis, melanocytes produce melanin, which is a pigment found in the skin, eyes, hair, nasal cavity, and 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 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. [10]

Since the action spectrum of sunburn 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 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.

Both lightly and darkly pigmented skin contain similar numbers of melanocytes, [12] with difference in skin color due to differences the packing of eumelanin into the melanosomes of keratinocytes: 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 of eumelanin and pheomelanin. [13] Pigmentation including tanning is under hormonal control, including the MSH 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 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. [14] Albinism may be caused by a number of other genes as well, like OCA2, [15] SLC45A2, [16] TYRP1, [17] and HPS1 [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 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. [20] Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics with dendritic cells: branched morphology; phagocytic capabilities; presentation of antigens to T-cells; and production and release of cytokines. [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 from hematopoietic stem cells in the bone marrow. Melanocytes on the other hand originate from 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, [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 express MHC 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 as CD40 and ICAM1 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 including IL-1, IL-3, IL-6, IL-8, TNF-α, and TGF-β. [20] [21] Like other immune cells, melanocytes secrete these cytokines in response to activation of Pattern Recognition Receptors (PRRs) such as Toll Like Receptor 4 (TLR4) which recognize 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. [20]

Melanocytes are ideally positioned in the epidermis to be sentinels against harmful pathogens. They reside in the stratum basale, [23] the lowest layer of the epidermis, 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 both keratinocytes and Langerhans cells, [20] [21] both of which are also actively phagocytic, [23] 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-quinone 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. Increased melanin production is seen in conditions where adrenocorticotropic hormone (ACTH) is elevated, such as 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. [25]

Melanosomes are 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 [26] and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.

Stem cells

The 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 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. [27]

Clinical significance

See also

Related Research Articles

<span class="mw-page-title-main">Human skin color</span>

Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics, exposure to the sun, disorders, or some combination thereof. Differences across populations evolved through natural selection or sexual selection, because of social norms and differences in environment, as well as regulations of the biochemical effects of ultraviolet radiation penetrating the skin.

<span class="mw-page-title-main">Melanin</span> Group of natural pigments found in most organisms

Melanin is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes.

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, which happens every 40 to 56 days in humans.

<span class="mw-page-title-main">Epidermis</span> Outermost of the three layers that make up the skin

The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.

The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating hormone (β-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland.

<span class="mw-page-title-main">Melanosome</span> Organelle found in animal cells used for the synthesis, storage and transport of melanin

A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotection in animal cells and tissues.

<span class="mw-page-title-main">Hyperpigmentation</span> Skin condition

Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.

<span class="mw-page-title-main">Tyrosinase</span> Enzyme for controlling the production of melanin

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.

<span class="mw-page-title-main">Skin whitening</span> Practice of using chemical substances to lighten the skin

Skin whitening, also known as skin lightening and skin bleaching, is the practice of using chemical substances in an attempt to lighten the skin or provide an even skin color by reducing the melanin concentration in the skin. Several chemicals have been shown to be effective in skin whitening, while some have proven to be toxic or have questionable safety profiles. This includes mercury compounds which may cause neurological problems and kidney problems.

<span class="mw-page-title-main">Human skin</span> Organ covering the outside of the human body

The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals' skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin: hairy and glabrous skin (hairless). The adjective cutaneous literally means "of the skin".

<span class="mw-page-title-main">Smoker's melanosis</span> Medical condition

Smoker's melanosis is seen with the naked eye as a brown to black pigmentation of the oral tissue i.e. the gums, cheeks or palate as well as in larynx. It is most often seen in the lower labial gingiva of tobacco users. Most easily it is found in Caucasians, due to their lack of a genetically caused melanin pigmentation.

<span class="mw-page-title-main">PMEL (gene)</span> Protein-coding gene in humans

Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.

<span class="mw-page-title-main">TYRP1</span> Enzyme

Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene.

<span class="mw-page-title-main">Membrane-associated transporter protein</span> Protein

Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene.

Pigmentation disorders are disturbances of human skin color. There may be a loss or reduction, which may be related to loss of melanocytes or the inability of melanocytes to produce melanin or transport melanosomes correctly.

Oculocutaneous albinism type I or type 1A is form of the autosomal recessive condition oculocutaneous albinism that is caused by a dysfunction in the gene for tyrosinase.

<span class="mw-page-title-main">Ocular albinism type 1</span> Most common type of ocular albinism

Ocular albinism type 1(OA1) is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in Oa1. Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.

<span class="mw-page-title-main">Amelanism</span> Pigmentation abnormality

Amelanism is a pigmentation abnormality characterized by the lack of pigments called melanins, commonly associated with a genetic loss of tyrosinase function. Amelanism can affect fish, amphibians, reptiles, birds, and mammals including humans. The appearance of an amelanistic animal depends on the remaining non-melanin pigments. The opposite of amelanism is melanism, a higher percentage of melanin.

Oral pigmentation is asymptomatic and does not usually cause any alteration to the texture or thickness of the affected area. The colour can be uniform or speckled and can appear solitary or as multiple lesions. Depending on the site, depth, and quantity of pigment, the appearance can vary considerably.

<span class="mw-page-title-main">Dark skin</span> Human skin color

Dark skin is a type of human skin color that is rich in melanin pigments. People with dark skin are often referred to as black people, although this usage can be ambiguous in some countries where it is also used to specifically refer to different ethnic groups or populations.

References

  1. ↑ "Melanocyte". Lexico UK English Dictionary. Oxford University Press. Archived from the original on 2020-03-22.
  2. ↑ "Melanocyte". Merriam-Webster.com Dictionary .
  3. ↑ Cramer SF (February 1991). "The origin of epidermal melanocytes. Implications for the histogenesis of nevi and melanomas". Archives of Pathology & Laboratory Medicine. 115 (2): 115–9. PMID   1992974.
  4. ↑ Barden H, Levine S (June 1983). "Histochemical observations on rodent brain melanin". Brain Research Bulletin. 10 (6): 847–51. doi:10.1016/0361-9230(83)90218-6. PMID   6616275. S2CID   4783099.
  5. ↑ Markert CL, Silvers WK (May 1956). "The Effects of Genotype and Cell Environment on Melanoblast Differentiation in the House Mouse". Genetics. 41 (3): 429–50. doi:10.1093/genetics/41.3.429. PMC   1209793 . PMID   17247639.
  6. ↑ Mayeaux EJ, Cox JT, et al. (American Society for Colposcopy and Cervical Pathology) (2011-12-28). Modern Colposcopy Textbook and Atlas. Lippincott Williams & Wilkins. ISBN   9781451153835.
  7. ↑ Mintz B (1971). "Clonal basis of mammalian differentiation". Symposia of the Society for Experimental Biology. 25: 345–70. PMID   4940552.
  8. ↑ Nichols SE, Reams WM (March 1960). "The occurrence and morphogenesis of melanocytes in the connective tissues of the PET/MCV mouse strain". Journal of Embryology and Experimental Morphology. 8: 24–32. PMID   14426921.
  9. ↑ Theriault LL, Hurley LS (October 1970). "Ultrastructure of developing melanosomes in C57 black and pallid mice". Developmental Biology. 23 (2): 261–75. doi:10.1016/0012-1606(70)90098-9. PMID   5476812.
  10. ↑ Agar N, Young AR (April 2005). "Melanogenesis: a photoprotective response to DNA damage?". Mutation Research. 571 (1–2): 121–32. doi:10.1016/j.mrfmmm.2004.11.016. PMID   15748643.
  11. ↑ Parrish JA, Jaenicke KF, Anderson RR (August 1982). "Erythema and melanogenesis action spectra of normal human skin". Photochemistry and Photobiology. 36 (2): 187–91. doi:10.1111/j.1751-1097.1982.tb04362.x. PMID   7122713. S2CID   38940583.
  12. ↑ Tadokoro, Taketsugu; Yamaguchi, Yuji; Batzer, Jan; Coelho, Sergio G.; Zmudzka, Barbara Z.; Miller, Sharon A.; Wolber, Rainer; Beer, Janusz Z.; Hearing, Vincent J. (2005). "Mechanisms of Skin Tanning in Different Racial/Ethnic Groups in Response to Ultraviolet Radiation". Journal of Investigative Dermatology. 124 (6). Elsevier BV: 1326–1332. doi: 10.1111/j.0022-202x.2005.23760.x . ISSN   0022-202X. PMID   15955111.
  13. 1 2 Greaves, Mel (2014-04-22). "Was skin cancer a selective force for black pigmentation in early hominin evolution?". Proceedings of the Royal Society B: Biological Sciences. 281 (1781): 20132955. doi: 10.1098/rspb.2013.2955 . ISSN   0962-8452. PMC   3953838 . PMID   24573849.
  14. ↑ "TYR". National Institutes of Health. Retrieved 23 June 2013.
  15. ↑ "OCA2". National Institutes of Health. Retrieved 25 March 2016.
  16. ↑ "SLC45A2". National Institutes of Health. Retrieved 25 March 2016.
  17. ↑ "TYRP1". National Institutes of Health. Retrieved 25 March 2016.
  18. ↑ "HPS1". National Institutes of Health. Retrieved 25 March 2016.
  19. ↑ Montoliu L, Grønskov K, Wei AH, Martínez-García M, Fernández A, Arveiler B, Morice-Picard F, Riazuddin S, Suzuki T, Ahmed ZM, Rosenberg T, Li W (January 2014). "Increasing the complexity: new genes and new types of albinism". Pigment Cell & Melanoma Research. 27 (1): 11–8. doi: 10.1111/pcmr.12167 . PMID   24066960. S2CID   7305884.
  20. 1 2 3 4 5 6 Gasque P, Jaffar-Bandjee MC (October 2015). "The immunology and inflammatory responses of human melanocytes in infectious diseases". The Journal of Infection. 71 (4): 413–21. doi:10.1016/j.jinf.2015.06.006. PMID   26092350.
  21. 1 2 3 4 5 Plonka PM, Passeron T, Brenner M, Tobin DJ, Shibahara S, Thomas A, Slominski A, Kadekaro AL, Hershkovitz D, Peters E, Nordlund JJ, Abdel-Malek Z, Takeda K, Paus R, Ortonne JP, Hearing VJ, Schallreuter KU (September 2009). "What are melanocytes really doing all day long...?". Experimental Dermatology. 18 (9): 799–819. doi:10.1111/j.1600-0625.2009.00912.x. PMC   2792575 . PMID   19659579.
  22. ↑ Mackintosh JA (July 2001). "The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin". Journal of Theoretical Biology. 211 (2): 101–13. Bibcode:2001JThBi.211..101M. doi:10.1006/jtbi.2001.2331. PMID   11419954.
  23. 1 2 3 Abdallah F, Mijouin L, Pichon C (2017). "Skin Immune Landscape: Inside and Outside the Organism". Mediators of Inflammation. 2017: 5095293. doi: 10.1155/2017/5095293 . PMC   5664322 . PMID   29180836.
  24. ↑ Tapia CV, Falconer M, Tempio F, Falcón F, López M, Fuentes M, Alburquenque C, Amaro J, Bucarey SA, Di Nardo A (July 2014). "Melanocytes and melanin represent a first line of innate immunity against Candida albicans". Medical Mycology. 52 (5): 445–54. doi: 10.1093/mmy/myu026 . PMID   24934806.
  25. ↑ Abdel-Malek Z, Scott MC, Suzuki I, Tada A, Im S, Lamoreux L, Ito S, Barsh G, Hearing VJ (2000-01-01). "The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation". Pigment Cell Research. 13 (Suppl 8): 156–62. doi:10.1034/j.1600-0749.13.s8.28.x. PMID   11041375.
  26. ↑ Eller MS, Maeda T, Magnoni C, Atwal D, Gilchrest BA (November 1997). "Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12627–32. Bibcode:1997PNAS...9412627E. doi: 10.1073/pnas.94.23.12627 . PMC   25061 . PMID   9356500.
  27. ↑ Cichorek M, Wachulska M, Stasiewicz A, Tymińska A (February 2013). "Skin melanocytes: biology and development". Postepy Dermatologii I Alergologii. 30 (1): 30–41. doi:10.5114/pdia.2013.33376. PMC   3834696 . PMID   24278043.

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