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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/L1286    most recent 00187.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Guedes, A. G. P. Articles by Kannan, M. S. Search for Related Content PubMed PubMed Citation Articles by Guedes, A. G. P. Articles by Kannan, M. S.

CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge

Departments of ¹Veterinary Clinical Sciences, ²Veterinary and Biomedical Sciences, ³Veterinary Population Medicine, and ⁶Pediatrics, University of Minnesota, St. Paul, Minnesota; ⁴Trudeau Institute, Saranac Lake, New York; and ⁵Department of Medicine and Immunology, Mayo Clinic, Rochester, Minnesota

Submitted 30 May 2006 ; accepted in final form 1 August 2006

The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 µg of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (R_L) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced R_L were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists.

interleukin-13; inflammation; asthma; eosinophil; airway smooth muscle

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