Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identi?es a severe, nonatopic subset of patients

Portelli, Michael A.; Moseley, C.; Stewart, Ceri E.; Postma, Dirkje S.; Howarth, P.; Warner, J.A.; Holloway, J.W.; Koppelman, Gerard H.; Sayers, Ian

Abstract

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studieshave identi?ed uPAR elevation in asthma; however, a de?nitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.
Objectives: We aimed to comprehensively determine the uPAR expression pro?lein asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features.
Methods: uPAR levels were determined in control (n = 9) and asthmatic (n = 27)bronchial biopsies using immunohistochemistry, with a semi-quantitative score de?ning intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels weredetermined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.Measurements and main results: In bronchial tissue, uPAR was elevated inin?ammatory cells in the lamina propria (P = 0.0019), bronchial epithelial(P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identi?ed. scuPAR serum levels were elevated in patients with asthma (1.5-f old; P = 0.0008), and we identi?ed an association between high uPAR serum levels and severe, nonatopic disease.
Conclusions: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The ?ndings warrant further investigation and may provide a therapeutic opportunity for this refractory population.

Citation

Portelli, M. A., Moseley, C., Stewart, C. E., Postma, D. S., Howarth, P., Warner, J., …Sayers, I. (in press). Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients. Allergy, https://doi.org/10.1111/all.13046

• Journal Article Type: Article
• Acceptance Date: Sep 9, 2016
• Online Publication Date: Oct 5, 2016
• Deposit Date: Jan 30, 2017
• Publicly Available Date: Jan 30, 2017
• Journal: Allergy
• Print ISSN: 0105-4538
• Electronic ISSN: 1398-9995
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/all.13046
• Public URL: https://nottingham-repository.worktribe.com/output/824634
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/all.13046/abstract