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-couple d receptors that are activated after proteolytic cleavage of the amino term inus of the receptor, are likely to play a major role in airway inflammatio n. 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 inflam ed airways. Objective: The purpose of this study was to compare the expression and dist ribution of PARs in biopsy specimens obtained from asthmatic and normal sub jects and to examine the effect of inhaled corticosteroids on PAR expressio n. Methods: Biopsy specimens were obtained from 10 normal and 20 asthmatic pat ients, and sections were stained for PAR-1, -2, -3, and -4 through use of s pecific antibodies. Staining was scored semiquantitatively for both intensi ty 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 epithe lium, PAR-1 and -3 staining appeared to be apically concentrated, whereas P AR-2 and -4 staining was more diffuse. In normal subjects, epithelial stain ing 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 su bjects was similar to that in specimens from normal subjects, irrespective of whether the former were using inhaled corticosteroids. However, PAR-2 st aining in asthmatic epithelium was significantly increased in comparison wi th normal epithelium. Expression of PARs in airway smooth muscle did not di ffer between groups. Conclusion: Asthma per se is associated with increased PAR-2 expression in bronchial epithelium. Importantly, staining was not influenced by inhaled c orticosteroids. These results suggest that PAR-2 might be involved in airwa y inflammation.