Proteinase-activated receptor-2 (PAR-2) expression on inflammatory cells in severe asthma
Bibliographic record
Abstract
PAR-2, a G-coupled receptor activated by serine proteinases, is widely expressed in the human body and is involved in inflammation. We have shown that PAR-2 activation in the airways plays a pathogenetic role in mouse models of asthma. PAR-2 expression is increased in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells of asthmatic individuals has not been. Severe asthma has different phenotypic characteristics from mild-moderate disease. In this study we compared PAR-2 expression on immune cells between subjects with mild/moderate and severe asthma. A total of 36 asthma subjects (24 mild/moderate; 12 severe by ATS guidelines) were recruited at the University of Alberta Hospital and peripheral blood obtained. PAR-2 expression was analyzed by flow cytometry and qRT-PCR in whole blood. There were no differences in the % of eosinophils, neutrophils or CD4+ T cells expressing PAR-2 between severe and mild/moderate asthmatics. CD14 monocytes were classified as classical (CD14++CD16-) or intermediate (CD14++CD16+). No difference in total numbers of either monocyte sub-population was noted between the two asthma groups. More intermediate monocytes from patients with severe asthma (33.6±5.1%) expressed PAR-2 compared to patients with mild/moderate asthma (22.4±4.0%, p=0.039), but there was no difference between asthma phenotypes in the percent of classical monocytes expressing PAR-2 (11.7±2.8% vs. 12.5±2.9%). PAR-2 mRNA expression was not different between severe and mild/moderate asthmatics, however, PAR-2 mRNA correlated with total dose of inhaled steroids and inversely correlated with % predicted FEV1. PAR-2 expression is increased on intermediate monocytes in subjects with severe asthma. Intermediate monocytes are pro-inflammatory and their numbers are increased in inflammatory diseases. Our data suggest that PAR-2-mediated activation of intermediate monocytes may play a role in the pathogenesis of severe asthma, although the effects of PAR-2-mediated activation of these cells are not known.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".