Epidermal Keratinocytes from Light vs. Dark Skin Exhibit Differential Degradation of Melanosomes

Abstract

Modification of skin complexion coloration has traditionally been accomplished by interruption or attenuation of melanogenesis and/or melanosome transfer. Post-transfer modification of pigmented melanosomes provides an attractive and distinct avenue of modulating skin pigmentation. The processing of melanosomes during keratinocyte (KC) terminal differentiation and the degradative variability observed between light and dark skin (LS and DS) remains enigmatic. To evaluate this, we developed a model system to investigate the loss of fluorescently labeled and isolated melanosomes by cultured human KCs. The extent of melanosome loss has been qualitatively assessed using transmission electron microscopy and indirect immunofluorescence with confocal microscopy, and quantitatively assessed using flow cytometry analysis. Results show that melanosomes are incorporated into the cytoplasm of both light and dark keratinocytes (LKCs and DKCs) and trafficked to a perinuclear region. Within 48 hours, confocal microscopy images suggest that LKCs display accelerated melanosome loss. This time-dependent decrease in carboxyfluorescein diacetate (CFDA) fluorescence was then quantitatively analyzed using flow cytometry. Consistent with the results of the confocal analysis, over a 48-hour time frame, LKCs appear to lose melanosomes more efficiently than DKCs. These experiments show that melanosomes are more rapidly lost in KCs derived from LS as opposed to DS.

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

“…In white skin, melanosomes are small, not very heavily pigmented and form membrane-bound clusters in the keratinocytes that are eventually degraded generating 'melanin dust' in suprabasal layers of the skin. [7] In black skin, melanosomes are large and remain as single organelles throughout the skin, while both forms are found in Asian skin. [8] Over a hundred genes are thought to play a role in melanin synthesis and melanocyte function; however, only 11 have been confirmed as key determinants of normal skin pigment variation through genome-wide association studies to date, [9] with some genes linked exclusively to either inter-or intra-population variation.…”

Age-Related Hair Pigment Loss

“…Melanocytes are also likely to influence keratinocytes in other more generic, nonpigmentary ways. As very stable and long-living sentinel dendritic cells of the skin, melanocytes produce a wide range of regulatory cytokines, growth factors, eicosanoids, adhesion molecules, and extracellular matrix molecules, and these will influence the behavior of neighboring keratinocytes [49,50]. The reduction or absence of these bio-response modifiers in the canities-affected HF is therefore most likely to have implications for the highly active matrix keratinocytes in this HF compartment.…”

“…There has long been intense research interest into the nature of melanocyte-keratinocyte crosstalk in the epidermis [2,49,50], and with the advent of in vitro and ex vivo culture models for HFs, attention has also been turning to the nature of the cellular partnerships in HFs [51]. Evidence from mixed skin phototype-origin melanocytes and keratinocytes suggests that the keratinocyte partner directs the melanocyte to produce the type of melanin matching the keratinocyte donor's skin phototype [49,50]. Similarly, melanin transfer to the keratinocyte appears to reduce its proliferative potential and thus may stimulate terminal differentiation.…”

Large Melanosome Complex Is Increased in Keratinocytes of Solar Lentigo

“…These morphological changes of melanocytes are consistent with increased melanization due to the differentiation of melanocytes in the SL lesions. The melanosome complexes in keratinocytes are digested by lysosomal enzymes in the process of cornification, and most melanosomes are decomposed by formation of a stratum corneocyte [24][25][26]. If the diameter of a melanosome complex decreases than 400 nm, it will not be observed optically.…”