Title: Airway responsiveness in CD38-deficient mice in allergic airway disease: studies with bone marrow chimeras.
Authors: Guedes, Alonso G P; Jude, Joseph A; Paulin, Jaime; Rivero-Nava, Laura; Kita, Hirohito; Lund, Frances E; Kannan, Mathur S
Published In Am J Physiol Lung Cell Mol Physiol, (2015 Mar 01)
Abstract: CD38 is a cell-surface protein involved in calcium signaling and contractility of airway smooth muscle. It has a role in normal airway responsiveness and in airway hyperresponsiveness (AHR) developed following airway exposure to IL-13 and TNF-α but appears not to be critical to airway inflammation in response to the cytokines. CD38 is also involved in T cell-mediated immune response to protein antigens. In this study, we assessed the contribution of CD38 to AHR and inflammation to two distinct allergens, ovalbumin and the epidemiologically relevant environmental fungus Alternaria. We also generated bone marrow chimeras to assess whether Cd38(+/+) inflammatory cells would restore AHR in the CD38-deficient (Cd38(-/-)) hosts following ovalbumin challenge. Results show that wild-type (WT) mice develop greater AHR to inhaled methacholine than Cd38(-/-) mice following challenge with either allergen, with comparable airway inflammation. Reciprocal bone marrow transfers did not change the native airway phenotypic differences between WT and Cd38(-/-) mice, indicating that the lower airway reactivity of Cd38(-/-) mice stems from Cd38(-/-) lung parenchymal cells. Following bone marrow transfer from either source and ovalbumin challenge, the phenotype of Cd38(-/-) hosts was partially reversed, whereas the airway phenotype of the WT hosts was preserved. Airway inflammation was similar in Cd38(-/-) and WT chimeras. These results indicate that loss of CD38 on hematopoietic cells is not sufficient to prevent AHR and that the magnitude of airway inflammation is not the predominant underlying determinant of AHR in mice.
PubMed ID: 25575514
MeSH Terms: ADP-ribosyl Cyclase 1/deficiency*; ADP-ribosyl Cyclase 1/metabolism; Administration, Inhalation; Allergens/immunology; Animals; Bone Marrow Transplantation*; Bone Marrow/metabolism; Bronchial Hyperreactivity/complications; Bronchial Hyperreactivity/pathology*; Bronchial Hyperreactivity/therapy*; Bronchoalveolar Lavage Fluid/cytology; Cell Count; Chemokines/metabolism; Chimera/immunology*; Lung/pathology; Lung/physiopathology; Methacholine Chloride/administration & dosage; Mice, Inbred C57BL; Ovalbumin/immunology; Pneumonia/complications; Pneumonia/pathology; Respiratory Hypersensitivity/complications; Respiratory Hypersensitivity/pathology*; Respiratory Hypersensitivity/therapy*