Merkel cells as putative regulatory cells in skin disorders: an in vitro study.
Bottom Line: However, neither proliferation nor reactions to the epidermal environment have been demonstrated.Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs.We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated.
Affiliation: University of Brest, EA4326, Brest, France.
Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca(2+)-independent, as inhibition of Ca(2+) channels or culture in the absence of Ca(2+) failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated.
Related in: MedlinePlus
Mentions: MCs are rare neuroendocrine cells of the epidermis. Due to their rarity, a great challenge to their study is the harvest of a sufficient number of cells to perform experiments. A significant advance was achieved by the purification of GFP-positive MCs from transgenic mice , , but this method remains restrictive for most laboratories. Here, we used a positive magnetic cell sorting strategy to enrich for MCs. The swine snout was preferred to human biopsies for its higher proportion of MCs as demonstrated by CK20 immunostaining (Figure 1).