Proteinase-activated receptor-1 and 2 expression in the bronchial epithelium

Introduction: Proteinase-activated receptor-1 (PAR-1) and 2 (PAR-2) mediate the interplay between coagulation, inflammation and tissue remodelling. There is also accumulating evidence supporting the importance of these receptors in the context of chronic obstructive pulmonary disease, asthma and fibroproliferative lung conditions such as idiopathic pulmonary fibrosis. However the expression and localization of these receptors in the bronchial epithelium remains unclear. Aims: In this study we investigated the expression and localization of PAR-1 and 2 in normal human bronchial epithelium. Methods: Human small airways were formaldehyde-fixed and paraffin-embedded or snap frozen. Immunohistochemistry with monoclonal antibodies for PAR-1 and 2 was performed on longitudinal sections using the avidin-biotin antibody complexing method on paraffin sections and a 2-step polymer detection system on frozen sections. Primary human bronchial epithelial cells (HBECs) were isolated from fresh lung tissue and cultured at air liquid interface after 2 weeks in submerged culture. Expression of PAR-1 and 2 was assessed by immunocytofluorescence and qPCR. Results: Immunohistochemistry using human bronchial epithelium from healthy individuals and studies employing HBECs revealed that PAR-1 is only weakly expressed by basal cells. In contrast, PAR-2 is widely and highly expressed by all epithelial cell types, with highest expression localized to columnar ciliated cells. Conclusions: Our data indicate that PAR-2 is the main PAR receptor expressed by the human bronchial epithelium. These data have important implications for our understanding of the role of PARs in the context of bronchial inflammation and remodelling. Funded by BLF.