Recent studies have demonstrated that extracellular
adenosine 5'-triphosphate (eATP) is involved in allergic airway
inflammation by activating
purinergic receptors. eATP can be hydrolyzed by ectonucleotidases, such as CD39. In this study, we investigated the expression and distribution of CD39 in the lungs of mice, as well as the effects of
apyrase on airway
inflammation and the chemotactic migration of dendritic cells (DCs). A mouse model of
asthma was developed with chicken ovalbumin (OVA)/
aluminum hydroxide using female C57BL/6 mice.
Apyrase was administered to OVA-sensitized mice prior to each challenge by
intraperitoneal injection. The distribution of CD39 was detected by immunofluorescence. The
mRNA and
protein expression of CD39 was determined by quantitative PCR and western blot analysis, respectively. The levels of Th2
cytokines in the bronchoalveolar lavage fluid (BALF) were measured by
enzyme-linked
immunosorbent assay (ELISA). The effect of
apyrase on the chemotactic migration of DCs towards
ATP was explored by migration assay in vitro. In the lungs, CD39 was primarily located in the cytoplasm and cytomembrane of bronchial epithelial cells and CD39 expression was reduced in mice with allergic
asthma. Treatment with
apyrase markedly attenuated OVA-induced airway
inflammation, including peribronchial eosinophilic
inflammation and reduced the number of inflammatory cells, as well as the levels of
cytokines in BALF. Furthermore,
apyrase also markedly reduced the expression of GATA binding protein 3 (GATA3) and decreased the chemotactic migration of DCs towards
ATP.Our data demonstrate that a reduction in CD39 expression may be associated with the development of allergic airway
inflammation and that
apyrase alleviates airway
inflammation by decreasing the chemotactic migration of DCs towards eATP. Therefore, targeting at eATP or ectonucleotidases may provide a novel therapeutic approach for allergic
asthma.