What are melanocytesreallydoing all day long…?

Abstract

Everyone knows and seems to agree that melanocytes are there to generate melanin -an intriguing, but underestimated multipurpose molecule that is capable of doing far more than providing pigment and UV protection to skin (1). What about the cell that generates melanin, then? Is this dendritic, neural crestderived cell still serving useful (or even important) functions when no-one looks at the pigmentation of our skin and its appendages and when there is essentially no UV exposure? In other words, what do epidermal and hair follicle melanocytes do in their spare time -at night, under your bedcover? How much of the full portfolio of physiological melanocyte functions in mammalian skin has really been elucidated already? Does the presence or absence of melanoctyes matter for normal epidermal and ⁄ or hair follicle functions (beyond pigmentation and UV protection), and for skin immune responses? Do melanocytes even deserve as much credit for UV protection as conventional wisdom attributes to them? In which interactions do these promiscuous cells engage with their immediate epithelial environment and who is controlling whom? What lessons might be distilled from looking at lower vertebrate melanophores and at extracutaneous melanocytes in the endeavour to reveal the 'secret identity' of melanocytes? The current Controversies feature explores these far too infrequently posed, biologically and clinically important questions. Complementing a companion viewpoint essay on malignant melanocytes (2), this critical re-examination of melanocyte biology provides a cornucopia of old, but underappreciated concepts and novel ideas on the slowly emerging complexity of physiological melanocyte functions, and delineates important, thought-provoking questions that remain to be definitively answered by future research. Praeludium pigmentosumFor those uninformed, the skin is an inert plastic wrap nature provides to keep us in and everything else out. How mistaken they are! The skin, in particular the epidermis, is one of the most active of all tissues ⁄ organs.Nature wisely placed the capillary circulation in the dermis. The epidermis has no vascular circulation thereby minimizing the probability that toxic chemicals, bacteria or fungi that penetrate through the stratum corneum can diffuse into the blood stream. That does not leave the epidermis defenseless. The epidermis has proteins called defensins that have anti-microbial properties. There are Toll-like receptors that recognize invading organisms and incite a host response. Even more interesting, it is well known that keratinocytes are avidly phagocytic. They have the capacity to phagocytize the wandering, invasive fungi or bacteria and digest them. It is both interesting and important that a-MSH stimulates the ingestion of candida by keratinocytes. a-MSH has a wide array of activities, only one of which is to stimulate the synthesis of melanin. There are receptors for a-MSH on Langerhans cells and keratinocytes as well as melanocytes. It has the ability to suppress infla...

Melanocytes and Skin Immunity

“…Following tissue injury or infection, macrophages exhibit an inflammatory phenotype and secrete pro-inflammatory mediators such as tumor necrosis factor, NO, and interleukin-1, which participate in the activation of various antimicrobial mechanisms (Murray and Wynn, 2011). Melanocytes are also located in the upper layer of the dermis or in the hair follicle pigmentary unit where melanocytes and their products might communicate with other cells (Plonka et al, 2009). This is in line with our observation that certain soluble factors secreted by murine melanocytes may exert immunologcial influence on macrophage-mediated antiinfection immunity through cross talks with macrophages.…”

“…The strategic positioning of melanocytes in the epidermis offers opportunities to encounter potentially harmful stimuli from outside, and it raises the possibility that melanocytes respond to potentially hostile environmental insults in addition to ultraviolet radiation. The dendritic nature and large surface area of melanocytes, coupled with their strategic location in the superficial layers of skin, raise the possibility that they are immunologically important cells in the skin immune system (Lu et al, 2002;Plonka et al, 2009). Clinically, it is noteworthy that some infections of skin are more common in individuals with fair skin than in those with dark skin (Mackintosh, 2001).…”

“…Melanocytes and their production of melanin pigment (a process termed melanogenesis) have important roles in cutaneous physiology (Hearing, 2011). The most obvious and most studied function of melanocytes is to synthesize melanin that confers color on skin and hair, and protects epidermal cells from ultraviolet radiation-induced changes in DNA structure (Plonka et al, 2009). However, accumulating evidence has shown that melanocytes are also active factors in the skin immune system, participate in immune responses, and have immunomodulatory properties.…”

Oral Mucosal Melanoma: Some Pathobiological Considerations and an Illustrative Report of a Case

“…Melanocytes also have the capacity to produce melatonin and serotonin which appear to contribute to the regulation of the metabolic activities of neighbouring cells and thus to the homeostasis of skin and mucosa both under physiological conditions, and in response to noxious stimuli [30]. The functions of mucosal melanocytes in this regard are not well understood [12,31,32].…”

Clinical features of the head and neck mucosal melanoma. А review

“…Роль таких меланоцитов плохо изучена, однако имеются свидетельства их антимикробной и иммуно-логической активности, а именно антигенпрезентиро-вания и продукции цитокинов [12,13].…”