Patients with guttate psoriasis have been reported to respond to anticholinergic treatment. We wanted to know how the cholinergic system could be involved in this process. Mast cells are characteristic components of the inflammatory infiltrate of guttate psoriasis. We therefore studied the cholinergic system in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a mast cell line (HMC-1) using PCR. Both in vivo and in vitro, mast cells lacked expression of cholinacetyl transferase, vesicular acetylcholine transporter and choline transporter-1 but contained high levels of acetylcholinesterase and different nicotinic and muscarinic acetylcholine receptor (AChR). In lesional epidermis, both acetylcholine production and AChR expression was mostly shifted from the basal to the suprabasal layers. In vitro, acetylcholine, choline and nicotine, but not muscarine, induced mast cell degranulation but not LTB-4 or TNF-alpha secretion. This process could be inhibited by low doses of different nicotinic acetylcholine receptor antagonists.

In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC‐1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter‐1 (ChT‐1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (α3, α5, α7, α9, α10, β2 and β4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC‐1 cells all AChR subunits found in skin where present on mRNA level, except α7 and β2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic α3, α5, α9, β2 and β4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine.