Functional characterization and expression analysis of the proteinase-activated receptor-2 in human cutaneous mast cells.
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.
Department of Dermatology, IZKF Münster and Ludwig Boltzmann Institute for Cell- and Immunbiology of the Skin, University of Münster, Münster, Germany.
Corinna
C
Moormann
Metin
M
Artuc
Elena
E
Pohl
Georg
G
Varga
Jörg
J
Buddenkotte
Nathalie
N
Vergnolle
Randolf
R
Brehler
Beate M
BM
Henz
Stefan W
SW
Schneider
Thomas A
TA
Luger
Martin
M
Steinhoff
D002118:Calcium / Q000032:analysis / Q000378:metabolism; D005434:Flow Cytometry; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D044462:Receptors, Proteinase-Activated / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D053802:Tryptases
D012333:RNA, Messenger; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; D006632:Histamine; D012697:Serine Endopeptidases; D053802:Tryptases; D002118:Calcium