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

Abstract

peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients. AbstractRationale: 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. Objectives: 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. Measurements and main 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.Asthma, a chronic inflammatory airway disorder, is known to cause widespread variable airflow obstruction that is often reversible, spontaneously or with treatment, and presents with airway hyperresponsiveness (1). The urokinase plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein (2-4) translated from the gene PLAUR (4). uPAR has been associated with asthma at the biological and cellular level (5-8), with elevated uPAR Allergy 72 (2017) 473-482

Serum plasminogen activator urokinase receptor predicts elevated risk of acute respiratory distress syndrome in patients with sepsis and is positively associated with disease severity, inflammation and mortality

“…Of note, suPAR may also be an emerging biomarker for patients with lung diseases. Previous studies have revealed that it is also highly expressed in patients with COPD, asthma and inhalation trauma (33–35). Considering that suPAR may be involved in the development of inflammatory diseases and lung injury-associated pathologies, it was hypothesized that suPAR may have an important role in the development of ARDS in patients with sepsis.…”

TNF is required for TLR ligand–mediated but not protease-mediated allergic airway inflammation

“…RNA profiling of AECs revealed that the gene whose expression in these cells was most affected by the absence of TNFR1/2 was Plaur, which encodes uPAR, a serine protease receptor involved in the generation of plasmin from plasminogen. Previous genetic (34) and biological (43,44) evidence has strongly implicated uPAR in asthma, particularly in severe, nonatopic asthma. Our current work shows that Plaur expression in AECs is dependent on TNF signaling responses in those cells.…”

Self-seeding circulating tumor cells promote the proliferation and metastasis of human osteosarcoma by upregulating interleukin-8

“…IL-8 levels in the cell culture supernatants and serum samples were measured using commercially available ELISA kits (Abcam, UK ab214030). ELISA was performed according to a previously described protocol 40 . The assays were performed in triplicate.…”