Dermal Fibroblasts Internalize Phosphatidylserine-Exposed Secretory Melanosome Clusters and Apoptotic Melanocytes

Abstract

Pigmentation in the dermis is known to be caused by melanophages, defined as melanosome-laden macrophages. In this study, we show that dermal fibroblasts also have an ability to uptake melanosomes and apoptotic melanocytes. We have previously demonstrated that normal human melanocytes constantly secrete melanosome clusters from various sites of their dendrites. After adding secreted melanosome clusters collected from the culture medium of melanocytes, time-lapse imaging showed that fibroblasts actively attached to the secreted melanosome clusters and incorporated them. Annexin V staining revealed that phosphatidylserine (PtdSer), which is known as an ‘eat-me’ signal that triggers the internalization of apoptotic cells by macrophages, is exposed on the surface of secreted melanosome clusters. Dermal fibroblasts were able to uptake secreted melanosome clusters as did macrophages, and those fibroblasts express TIM4, a receptor for PtdSer-mediated endocytosis. Further, co-cultures of fibroblasts and melanocytes demonstrated that dermal fibroblasts internalize PtdSer-exposed apoptotic melanocytes. These results suggest that not only macrophages, but also dermal fibroblasts contribute to the collection of potentially toxic substances in the dermis, such as secreted melanosome clusters and apoptotic melanocytes, that have been occasionally observed to drop down into the dermis from the epidermis.

Exploration of potential lipid biomarkers for age‐induced hair graying by lipidomic analyses of hair shaft roots with follicular tissue attached

“…Glucosylceramide and GalCer are considered to be biologically regulated lipids. In the epidermis, GalCer activates epidermal/3‐GluCer'ase and leads to an increase in Cer levels, ultimately promoting the formation of the skin barrier 14 . No relevant studies on the involvement of GalCer in melanin synthesis were found, and it is speculated that the difference in GalCer content in this study is related to the involvement of both GlcCer and GalCer in ceramide synthesis in sphingolipid metabolism (Figure 4B).…”

“…These melanosomes display apoptotic signals and are exposed on the surface of the secreted melanosome clusters. 14 PS is externalized, which may be a mechanism to resist cellular damage during melanin synthesis to delay the death promoted by melanin synthesis. 15 In our study, the PS content was found to be significantly higher in black hair than in white hair, which may be due to increased apoptosis of melanocytes in the hair follicle during melanin synthesis, leading to PS externalization and triggering a mechanism of resistance to cellular damage.…”

Melanin accumulation in dermal stem cells deteriorates their exosome‐mediated skin basement membrane construction in solar lentigo

“…Additionally, CD271‐negative and CD163‐negative cells that incorporated melanin were identified in about 20% of SL lesions. In vitro experiments have also shown melanin uptake in fibroblasts, 15 suggesting that the majority of these cells are dermal fibroblasts, which are abundant in the dermis layer. There are also CD163‐negative, CD68‐positive and weakly phagocytic macrophages in the dermis, which may uptake melanin.…”

“…These melanin‐phagocytosing macrophages are termed melanophages and are also known to be frequently present in benign melanocytic nevi and malignant melanomas, 14 but detailed studies have not been conducted. Recent in vitro studies have reported the phenomenon of melanin uptake by dermal fibroblasts, 15 raising the possibility that cells other than macrophages may be taking up melanin in the dermis of SL lesions. A possible mechanism for the accumulation of melanin in the dermis is the transit of melanosome‐containing globules secreted extracellularly by melanocytes 16,17 and melanosome‐containing keratinocyte fragments moving from the epidermis to the dermis 18 .…”

“…12,13 These melanin-phagocytosing macrophages are termed melanophages and are also known to be frequently present in benign melanocytic nevi and malignant melanomas, 14 but detailed studies have not been conducted. Recent in vitro studies have reported the phenomenon of melanin uptake by dermal fibroblasts, 15 raising the possibility that cells other than macrophages may be taking up melanin in the dermis of SL lesions.…”