Merkel cells as putative regulatory cells in skin disorders: an in vitro study.
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.
Boulais
Nicholas
N
University of Brest, EA4326, Brest, France.
Pereira
Ulysse
U
Lebonvallet
Nicolas
N
Gobin
Eric
E
Dorange
Germaine
G
Rougier
Nathalie
N
Chesne
Christophe
C
Misery
Laurent
L
D000818:Animals; D020013:Calcium Signaling; D049109:Cell Proliferation; D002478:Cells, Cultured; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D012871:Skin Diseases / Q000473:pathology*; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis
D014660:Vasoactive Intestinal Peptide