Allergic sensitization is oriented by CD73 enzyme

Increasing evidence suggests that extracellular adenosine is an important signaling nucleoside in the pathophysiology of bronchial asthma (1). CD73 is the key enzyme in the extracellular adenosine production (2). To date, very little is known about the role of CD73 enzyme in the development of allergic asthma. We aimed to investigate the contribution of CD73 in the assessment of allergic sensitization. Experiments were performed on wild type (wt) and CD73-deficient (CD73-/-) mice of both sexes. Groups of animals were sensitized to ovalbumin (OVA) by subcutaneous injection (100 mg/kg) on day 1 and day 8. 14 and 21 days following sensitization, mice were sacrificed to take main bronchi, pulmonary tissue and blood for functional, molecular and cellular studies. OVA sensitization induced a significant increase in CD73 bronchi expression and activity. Plasma IgE and pulmonary interleukin-4  levels tended to be higher in CD73-/- mice sensitized mice compared to wt mice. In addition, there was further increased of peribronchial inflammation and mucus production in CD73-/- sensitized mice. In vitro bronchial reactivity to carbachol of female non-sensitized wt mice was significant higher than bronchial reactivity of  male wt mice. This gender difference was abolished by in vitro tissue incubation with the CD73 inhibitor, adenosine 59-(a,s-methylene) diphosphate (APCP,100 µM) and, consistently, there was no gender difference in bronchial reactivity in CD73-/- mice. Our results demonstrate that CD73 actively regulates the assessment of allergic sensitization. References: 1 Cicala, C., Ialenti, A. Eur. J. Pharmacol; 2013, 714:522-525. 2 Zimmermann, H. Naunyn Schmiedebergs Arch.Pharmacol; 2000, 362:299-309.