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.
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Mentions: Therefore, we addressed the question of how such arrangements develop. Specific cell migrations were contested and MCs are thought to be terminally differentiated so they may not proliferate , , . In the present study, we tested the immunoreactivity of cultured MCs to the proliferation marker Ki-67. Unexpectedly, many cells were positive for both CK20 and Ki-67.All phases of mitosis were visible: prophase (Figure 5a), metaphase (Figure 5b), anaphase (Figure 5c, e) and telophase (Figure 5d, e). MCs were followed for over four weeks in culture, but proliferating CK20-positive cells were detected only during the first two weeks after enrichment. These results demonstrate for the first time that MCs can undergo mitosis in vitro. We supposed that keratinocyte factors disable this capability, which would explain why previous reports failed to amplify MCs.