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Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies 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

Authors

C. Moseley

Ceri E. Stewart

Dirkje S. Postma

P. Howarth

J.A. Warner

J.W. Holloway

Gerard H. Koppelman



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 identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.
Objectives: We aimed to comprehensively determine the uPAR expression profilein 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 defining 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 ininflammatory 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 identified. scuPAR serum levels were elevated in patients with asthma (1.5-f old; P = 0.0008), and we identified 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 findings 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 http://eprints.nottingham.ac.uk/id/eprint/40170
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/all.13046/abstract

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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