Characterization of Protease-activated Receptor-2 Immunoreactivity in Normal Human Tissues

Abstract

PAR-2 is a second member of a novel family of G-protein-coupled receptors characterized by a proteolytic cleavage of the amino terminus, thus exposing a tethered peptide ligand that autoactivates the receptor. The physiological and/or pathological role(s) of PAR-2 are still unknown. This study provides tissue-specific cellular localization of PAR-2 in normal human tissues by immunohistochemical techniques. A polyclonal antibody, PAR-2C, was raised against a peptide corresponding to the amino terminal sequence SLIGKVDGTSHVTGKGV of human PAR-2. Significant PAR-2 immunoreactivity was detected in smooth muscle of vascular and nonvascular origin and stromal cells from a variety of tissues. PAR-2 was also present in endothelial and epithelial cells independent of tissue type. Strong immunolabeling was observed throughout the gastrointestinal tract, indicating a possible function for PAR-2 in this system. In the CNS, PAR-2 was localized to many astrocytes and neurons, suggesting involvement of PAR-2 in neuronal function. A role for PAR-2 in the skin was further supported by its immunolocalization in the epidermis. PAR-2C antibody exemplifies an important tool to address the physiological role(s) of PAR-2.

Presence of functionally active protease‐activated receptors 1 and 2 in myenteric glia

“…Recently, PAR-1 expression has been reported in neurons of the ENS (Corvera et al 1999). PAR-2 is also widely expressed; it has been demonstrated in vascular tissue, the digestive system and epidermis (Al-Ani et al 1995 21 ; Santulli et al 1995;Derian and Eckardt 1997;D'Andrea et al 1998;Corvera et al 1999). Within the gastrointestinal tract, PAR-2 has been reported in enterocytes, smooth muscle cells and myenteric neurons.…”

Differential Expression of Protease-Activated Receptors-1 and -2 in Stromal Fibroblasts of Normal, Benign, and Malignant Human Tissues

“…Primary antibodies used in these experiments include the following: desmin (Dako, Carpinteria, CA), endothelial cell (CD31; Dako), fibroblast (prolyl 4-hydroxylase) (Dako), macrophage (CD68; Dako), mast cell tryptase (Dako), non-immuno serum (Vector Laboratories, Burlingame, CA), PAR-1 (The Robert Wood Johnson Pharmaceutical Research Institute (RWJPRI), Spring House, PA), [35][36][37] PAR-2 (RWJPRI), 33,35,38 smooth muscle actin (Dako), DNA topoisomerase II␣ (TOPO II␣) (Pharmingen, San Diego, CA) 39 and vimentin (Dako).…”

A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

“…17 PAR-2 is expressed in human lung epithelial cells, airway smooth muscle, 18 and fibroblasts 19 as well as in vascular smooth muscle and endothelial cells. 20 PAR-2 activation on airway epithelial cells causes the release of prostaglandin E2, 18 GM-CSF, eotaxin, 21 and matrix metalloproteinase-9. 22 PAR-2 expression is increased in respiratory epithelial cells of patients with asthma, 23 but the physiological role of PAR-2 in the airways remains unclear.…”