Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14(++)CD16(+) Peripheral Blood Monocytes of Patients with Severe Asthma

BACKGROUND: Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. METHODS: We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. RESULTS: Subjects with severe asthma had higher PAR-2 expression on CD14(++)CD16(+) monocytes (intermediate monocytes) and also higher percentage of CD14(++)CD16(+)PAR-2(+) monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14(++)CD16(+)PAR-2(+) in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14(++)CD16(+) PAR-2(+) cells in peripheral blood compared to subjects without exacerbations. CONCLUSIONS: PAR-2 expression is increased on CD14(++)CD16(+) monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14(++)CD16(+) monocytes may play a role in the pathogenesis of severe asthma.