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Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with
Nami Shrestha Palikhe1, Drew Nahirney1, Cheryl Laratta1
1Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
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.
Insights
Protease-Activated Receptor-2 (PAR-2) is elevated on intermediate monocytes in severe asthma patients, potentially serving as a biomarker for disease severity and exacerbations.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Protease-Activated Receptor-2 (PAR-2) is a G protein-coupled receptor involved in inflammation.
- PAR-2 activation in airways contributes to allergic airway inflammation.
- While PAR-2 is upregulated in asthma epithelium, its role on inflammatory cells is unstudied.
Purpose of the Study:
- To investigate PAR-2 expression on blood inflammatory cells in patients with mild/moderate and severe asthma.
- To determine if PAR-2 expression correlates with asthma severity or exacerbation history.
Main Methods:
- Recruited 12 severe and 24 mild/moderate asthmatics.
- Collected demographic, medication, and asthma severity data.
- Analyzed PAR-2 expression on blood inflammatory cells using flow cytometry.
Main Results:
- Severe asthmatics showed higher PAR-2 expression on intermediate monocytes (CD14++CD16+).
- A higher percentage of intermediate monocytes expressing PAR-2 distinguished severe from mild/moderate asthma.
- Increased PAR-2+ intermediate monocytes correlated with a history of asthma exacerbations.
Conclusions:
- PAR-2 expression on peripheral blood intermediate monocytes is increased in severe asthma.
- PAR-2 on these monocytes may serve as a biomarker for asthma severity.
- PAR-2-mediated monocyte activation could contribute to severe asthma pathogenesis.
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