EOSINOPHILS ACTIVATE WNT-5A SIGNALING PATHWAY AND PROMOTE AIRWAY SMOOTH MUSCLE CELLS CONTRACTILITY IN ASTHMA

Abstract

Background. Airway eosinophilia is a prominent feature of asthma. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released. There are studies on eosinophil-induced changes of ASM activity while the exact role of eosinophil in ASM contractility in asthma remains unclear. Aim. To evaluate the effect of eosinophils on WNT-5a signaling pathway activation and ASM contractility in asthma. Methods. 5 allergic asthma patients (AA) and 5 healthy subjects (HS) were examined. Blood eosinophils were isolated using high-density centrifugation and magnetic separation. Individual combined cultures of eosinophils and healthy immortalized ASM cells were prepared. Contractility was evaluated using collagen gel method. For gene expression analysis ASM cells were lysed and total RNA purified after 24 h of incubation with eosinophils. Gene expression was evaluated using RT-qPCR analysis. Results. ASM cells contractility increased 5.7% after incubation with AA eosinophils compared to HS eosinophils (p<0.05). Genes expression of α-actin, WNT-5a, TGF-β1 was higher in ASM cells after incubation with AA eosinophils compared to HS eosinophils (accordingly: 1.6±0.1 vs. 1.0±0.2; 1.8±0.5 vs. 1.0±0.2; 2.1±0.6 vs. 1.1±0.3 folds over control; p<0.05). Conclusions. Eosinophils promote ASM cells contractility as well as α-actin gene expression and these changes may be induced via WNT-5a signaling pathway.