BACKGROUND: Mastocytosis is characterized by abnormal growth and accumulation of mast cells (MCs) in different organs. MCs have been shown to express receptors for neuropeptides. Furthermore, neuropeptides can activate MCs inducing cytokine production and MC mediator release, which further contribute to MC chemotaxis and stimulate the release of vasoactive peptides from sensory nerves. Thus, a contribution of neuropeptides to mastocytosis seems highly conceivable, but has not been investigated sufficiently yet. This study aimed to analyse blood levels of the neuropeptides substance P (SP), somatostatin (SST), vasoactive intestinal peptide (VIP), calcitonine gene--related peptide (CGRP) and expression of the SP receptor NK-1R in the skin of patients with mastocytosis (n = 46) compared to healthy controls (n = 69). METHODS: Substance P, SST, VIP and CGRP plasma levels were analysed by ELISA, serum tryptase levels with the UniCAP System and NK-1R expression in the skin by immunohistochemistry. RESULTS: Plasma levels of SP (P < 0.0001), SST, (P = 0.007), VIP (P < 0.0001) and CGRP (P = 0.003) were significantly increased in patients with mastocytosis compared to controls. Tryptase serum levels correlated significantly with neuropeptide levels, implying a link between MC load and neuropeptide blood levels in mastocytosis. NK-1R was expressed on the majority of MCs, and NK-1R-positive cells were increased in lesional mastocytosis skin compared to control skin (P = 0.01). CONCLUSIONS: Elevated blood levels of the neuropeptides SP, SST, VIP and CGRP correlate with MC load and together with an increased expression of NK-1R in the skin of patients with mastocytosis indicate a role of neuropeptides in the pathophysiology of mastocytosis.
BACKGROUND:Mastocytosis is characterized by abnormal growth and accumulation of mast cells (MCs) in different organs. MCs have been shown to express receptors for neuropeptides. Furthermore, neuropeptides can activate MCs inducing cytokine production and MC mediator release, which further contribute to MC chemotaxis and stimulate the release of vasoactive peptides from sensory nerves. Thus, a contribution of neuropeptides to mastocytosis seems highly conceivable, but has not been investigated sufficiently yet. This study aimed to analyse blood levels of the neuropeptides substance P (SP), somatostatin (SST), vasoactive intestinal peptide (VIP), calcitonine gene--related peptide (CGRP) and expression of the SP receptor NK-1R in the skin of patients with mastocytosis (n = 46) compared to healthy controls (n = 69). METHODS:Substance P, SST, VIP and CGRP plasma levels were analysed by ELISA, serum tryptase levels with the UniCAP System and NK-1R expression in the skin by immunohistochemistry. RESULTS: Plasma levels of SP (P < 0.0001), SST, (P = 0.007), VIP (P < 0.0001) and CGRP (P = 0.003) were significantly increased in patients with mastocytosis compared to controls. Tryptase serum levels correlated significantly with neuropeptide levels, implying a link between MC load and neuropeptide blood levels in mastocytosis. NK-1R was expressed on the majority of MCs, and NK-1R-positive cells were increased in lesional mastocytosis skin compared to control skin (P = 0.01). CONCLUSIONS: Elevated blood levels of the neuropeptides SP, SST, VIP and CGRP correlate with MC load and together with an increased expression of NK-1R in the skin of patients with mastocytosis indicate a role of neuropeptides in the pathophysiology of mastocytosis.
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