title: Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.
abstract: 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.
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nami
authors.initials: N
authors.lastname: Shrestha Palikhe
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Drew
authors.initials: D
authors.lastname: Nahirney
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Laratta
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Vivek Dipak
authors.initials: VD
authors.lastname: Gandhi
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Dilini
authors.initials: D
authors.lastname: Vethanayagam
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.|Alberta Asthma Center, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Bhutani
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Irvin
authors.initials: I
authors.lastname: Mayers
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.|Department of Pathology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cameron
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.|Alberta Asthma Center, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Harissios
authors.initials: H
authors.lastname: Vliagoftis
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D012372:ROC Curve; D044464:Receptor, PAR-2 / Q000097:blood / Q000235:genetics*; D017452:Receptors, IgG / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D044464:Receptor, PAR-2; D017452:Receptors, IgG