Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma.
BACKGROUND
Protease-activated receptors (PARs), which are G protein-coupled receptors that are activated after proteolytic cleavage of the amino terminus of the receptor, are likely to play a major role in airway inflammation. PARs are activated by endogenous proteases, including thrombin (PAR-1, -3, and -4) and tryptase (PAR-2 and -4), both of which are present in inflamed airways.


OBJECTIVE
The purpose of this study was to compare the expression and distribution of PARs in biopsy specimens obtained from asthmatic and normal subjects and to examine the effect of inhaled corticosteroids on PAR expression.


METHODS
Biopsy specimens were obtained from 10 normal and 20 asthmatic patients, and sections were stained for PAR-1, -2, -3, and -4 through use of specific antibodies. Staining was scored semiquantitatively for both intensity and distribution.


RESULTS
Staining for all PARs was seen on the epithelium and smooth muscle in biopsy specimens from both normal and asthmatic subjects. In the epithelium, PAR-1 and -3 staining appeared to be apically concentrated, whereas PAR-2 and -4 staining was more diffuse. In normal subjects, epithelial staining intensity of PAR-1 and -3 was significantly greater than for PAR-4 (P < .05). Staining for PAR-1, -3, and -4 in biopsy specimens from asthmatic subjects was similar to that in specimens from normal subjects, irrespective of whether the former were using inhaled corticosteroids. However, PAR-2 staining in asthmatic epithelium was significantly increased in comparison with normal epithelium. Expression of PARs in airway smooth muscle did not differ between groups.


CONCLUSIONS
Asthma per se is associated with increased PAR-2 expression in bronchial epithelium. Importantly, staining was not influenced by inhaled corticosteroids. These results suggest that PAR-2 might be involved in airway inflammation.
Knight
D A
DA
Asthma and Allergy Research Institute Inc, Nedlands, Western Australia, Australia.
Lim
S
S
Scaffidi
A K
AK
Roche
N
N
Chung
K F
KF
Stewart
G A
GA
Thompson
P J
PJ
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D015854:Up-Regulation
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; C112908:protease-activated receptor 4