title: Airway responsiveness in CD38-deficient mice in allergic airway disease: studies with bone marrow chimeras.
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.
authors.affiliation: Department of Surgical and Radiological Sciences, University of California, Davis, California;
authors.forename: Alonso G P
authors.initials: AG
authors.lastname: Guedes
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jude
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota.
authors.forename: Jaime
authors.initials: J
authors.lastname: Paulin
authors.affiliation: Trudeau Institute, Saranac Lake, New York;
authors.forename: Laura
authors.initials: L
authors.lastname: Rivero-Nava
authors.affiliation: Departments of Immunology and Medicine, Mayo Clinic, Rochester, Minnesota;
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.affiliation: Trudeau Institute, Saranac Lake, New York; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota kanna001@umn.edu.
authors.forename: Mathur S
authors.initials: MS
authors.lastname: Kannan
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency* / Q000378:metabolism; D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000378:metabolism; D002678:Chimera / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D016210:Methacholine Chloride / Q000008:administration & dosage; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000473:pathology* / Q000628:therapy*
chemical_list: D000485:Allergens; D018925:Chemokines; D016210:Methacholine Chloride; D010047:Ovalbumin; D051997:ADP-ribosyl Cyclase 1
keywords: Alternaria; CD38; allergic airway disease; bone marrow chimeras