title: Apyrase protects against allergic airway inflammation by decreasing the chemotactic migration of dendritic cells in mice.
abstract: 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.
authors.affiliation: Department of Pneumology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pneumology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pneumology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pneumology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pneumology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000536:Aluminum Hydroxide; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D015398:Signal Transduction
chemical_list: D018927:Anti-Asthmatic Agents; D015703:Antigens, CD; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D000536:Aluminum Hydroxide; D000255:Adenosine Triphosphate; D010047:Ovalbumin; D001081:Apyrase; C067869:CD39 antigen