Eosinophil outer membrane integrins and IL-5, IL-3, GM-CSF receptors expression in severe eosinophilic asthma

Abstract

Introduction: severe eosinophilic asthma (SEA) has prominent inflammatory components that are characterized by pronounced eosinophilic infiltration. Eosinophil maturation and activation, as well as recruitment, are induced due to three main cytokines: interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte–macrophage colony-stimulating factor (GM-CSF) through their receptors and related with integrins activation states. However, there is a lack of information about the eosinophilic integrins and cytokines receptors expression in SEA. Aim: to investigate the expression of eosinophil α4β1, αMβ2 integrins and cytokines receptors (IL-5Rα, IL-3Rα, GM-CSFR) in SEA. Methods: we examined five stable SEA patients on high inhaled steroids dose and 11 steroids-free patients with allergic asthma (AA). Blood eosinophils were isolated using centrifugation and magnetic separation. Eosinophils were lyzed and mRNA was isolated. Gene expression of α4β1, αMβ2 integrins and IL-5Rα, IL-3Rα, GM-CSFR were analyzed using qRT-PCR. Results: expression of outer membrane integrins subunits was significantly increased in SEA group compared with AA group (αM – 3.1±1.6-fold, α4 – 1.8±0.2-fold, β1 – 2.5±0.5-fold, β2 – 2.1±0.9-fold; p<0.05). Moreover, IL-5Rα, IL-3Rα and GM-CSFR genes expression in SEA group was increased (IL-3Rα – 2.3±0.5-fold, IL-5Rα – 6.5±1.1-fold, GM-CSFR – 2.0±0.4-fold, p<0.05) compared with patients from AA group. Conclusion: eosinophils demonstrate higher expression of outer membrane integrins α4β1, αMβ2 and IL-5Rα, IL-3Rα, GM-CSFR in patients with SEA compared with AA.