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.
Highlights
Melanosomes are specialized organelles produced within melanocytes in which melanin pigment is synthesized after which they are transferred to different types of cells
We explored the possibility that fibroblasts are involved in dermal melanin pigmentation similar to melanosome-laden dermal melanophages and may reside for a long time in the dermis
In order to investigate how melanocytes produce and release extracellular packages containing multiple melanosomes, termed secretory melanosome clusters, normal human melanocytes were seeded on microporous membrane filters (Figure 1a) and were cultured for 6 days
Summary
Melanosomes are specialized organelles produced within melanocytes in which melanin pigment is synthesized after which they are transferred to different types of cells. Four possible mechanisms of melanosome transfer between melanocytes and keratinocytes have been proposed, that is, the cytophagocytosis model, the membrane fusion model, the shedding-phagocytosis model and the exocytosis-endocytosis model [1]. In 3 of those models, phagocytosis plays a pivotal role in the mechanism of melanosome transfer. Pigmentation in the dermis is known to be caused by melanophages containing melanosomes that have dropped down from the epidermis into the dermis in abnormal conditions such as severe inflammation. Melanosomes are thought to drop down into the dermis in cases when the basement membrane, a barrier against the invasion of foreign materials and a scaffolding for epidermal cells [3], is disrupted and loses its physiological function, which is often observed in inflammatory skin diseases such as Riehl’s melanosis, lichen planus pigmentosus and fixed drug eruptions [4,5,6]
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