Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients.
BACKGROUND
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 studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.


OBJECTIVE
We aimed to comprehensively determine the uPAR expression profile in 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 were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.


RESULTS
In bronchial tissue, uPAR was elevated in inflammatory 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-fold; 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.
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
M A
MA
Portelli
Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
C
C
Moseley
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
C E
CE
Stewart
Department of Pulmonology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
D S
DS
Postma
Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
P
P
Howarth
Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
J A
JA
Warner
Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK.
J W
JW
Holloway
Department of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
G H
GH
Koppelman
Glenfield Hospital, University of Leicester, Leicester, UK.
C
C
Brightling
Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
I
I
Sayers
D001249:Asthma / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D010641:Phenotype; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D012720:Severity of Illness Index
D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator
asthma; expression profile; urokinase plasminogen activator receptor