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

• Published in: PloS one Vol. 10; no. 12; p. e0144500
• Main Authors: Shrestha Palikhe, Nami, Nahirney, Drew, Laratta, Cheryl, Gandhi, Vivek Dipak, Vethanayagam, Dilini, Bhutani, Mohit, Mayers, Irvin, Cameron, Lisa, Vliagoftis, Harissios
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-12-2015; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Aged; Asthma; Asthma - blood; Asthma - diagnosis; Asthma - genetics; Asthma - pathology; Biomarkers; Biomarkers - blood; Blood; CD14 antigen; CD16 antigen; Cell activation; Cytometry; Demographics; Drug dosages; Epithelium; Female; Flow cytometry; Gene Expression; GPI-Linked Proteins - blood; GPI-Linked Proteins - genetics; Humans; Immunology; Inflammation; Influenza; Lipopolysaccharide Receptors - blood; Lipopolysaccharide Receptors - genetics; Male; Medicine; Middle Aged; Monocytes; Monocytes - metabolism; Monocytes - pathology; Par-2 protein; Pathogenesis; Patients; Peripheral blood; Primary Cell Culture; Protease; Receptor, PAR-2 - blood; Receptor, PAR-2 - genetics; Receptors, IgG - blood; Receptors, IgG - genetics; Respiratory tract; Respiratory tract diseases; Rheumatoid arthritis; ROC Curve; Serine; Severity of Illness Index; Edmonton Alberta Canada; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144500

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.
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.
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.
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.