Localization of protease-activated receptors-1 and-2 in human mast cells: Indications for an amplified mast cell degranulation cascade

Protease-activated receptors (PARs) belong to a family of G-coupled seven t ransmembrane receptors that are activated by a proteolytic cleavage of thei r N-termini, Recent studies suggest the involvement of protease-activated r eceptors-1 and -2 (PAR-1, PAR-2) activators in mast cell degranulation in v arious physiological and pathophysiological processes in inflammatory respo nses. Although PAR-1 and PAR-2 activating proteases, thrombin and tryptase, have been associated with mast cell activation, PAR-1 and PAR-2 have not b een localized within these cells. We describe here the localization of PAR- 1 and PAR-2 in mast cells from various normal human tissues using immunohis tochemical and double immunofluorescence techniques. The presence of these receptors on the membrane may explain the actions of accessible extracellul ar thrombin and tryptase for mast cell activation, In addition to the membr ane labeling, these receptors are also localized on the membrane of the int racellular tryptase-positive granules, which may function to sustain furthe r mast cell degranulation upon exocytosis, The localization of these two re ceptors in mast cells suggests a novel mechanism for controlling mast cell activation through regulation of PAR-1 and PAR-2.