1. ¹Department of Dermatology, IZKF Münster and Ludwig Boltzmann Institute for Cell- and Immunbiology of the Skin, University of Münster, Münster, Germany
2. ²Department of Experimental Dermatology, Charite University of Berlin, Berlin, Germany
3. ³Institute of Cell- and Neurobiology, Charite University of Berlin, Berlin, Germany
4. ⁴Department of Pharmacology, University of Calgary, Calgary, Canada

Correspondence: Dr Martin Steinhoff, Department of Dermatology, IZKF Münster and Ludwig Boltzmann Institute for Cell- and Immunbiology of the Skin, University of Münster, University Hospital Münster, von-Esmarch-Str. 58, Münster 48129, Germany. E-mail: msteinho@uni-muenster.de

⁵Both these authors contributed equally to this work.

Received 8 July 2005; Revised 26 October 2005; Accepted 12 November 2005; Published online 9 February 2006.

Abstract

Proteinase-activated receptor-2 (PAR₂) belongs to a new G protein-coupled receptor subfamily activated by serine proteinases. PAR₂ has been demonstrated to play a role during inflammation and immune response in different tissues including the skin. We examined whether PAR₂ is functionally expressed by cutaneous human primary skin mast cells (HPMC) and the human mast cell line 1 (HMC-1). Reverse transcription-polymerase chain reaction and FACS analysis show expression of PAR₂ both at the RNA and protein level. HPMCs and HMC-1 also express PAR₁, PAR₃, and PAR₄. Ca-mobilization studies demonstrate functional PAR₂ expressed by human skin mast cells, as shown by natural and synthetic PAR₂ agonists. PAR₂ agonists induced histamine release from HPMC indicating a role of PAR₂ in regulating inflammatory and immune responses by skin mast cells. Double-immunofluorescence staining reveals colocalization of PAR₂ with tryptase in the majority of human skin mast cells. In conclusion, trypsin and tryptase as well as specific agonists for PAR₂ were able to induce Ca²⁺ mobilization in HPMCs, and agonists of PAR₂ induce the release of histamine from these cells. Thus, PAR₂ may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity.