12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels

摘要

Background: Induction of 15-lipoxygenase-1 (15-LO-1) has been observed in the airways of subjects with asthma, although its physiologic role in the airways has remained largely undefined. Objectives: We sought to test the hypothesis that the mouse 15-LO-l ortholog 12/15-LO contributes to the development of allergic airways inflammation.Methods: Two models were used to evaluate wild-type and 12/15-LO-deficient mice. The systemic model involved intraperitoneal injections of allergen, and the mucosal model involved allergen exposures occurring exclusively in the airways. The systemic and mucosal-specific contributions of 12/15-LO to allergic sensitization and airways inflammation were determined by comparing the results obtained in the 2 models.Results: In the mucosal model 12/15-LO knockout mice were protected from the development of allergic sensitization and airways inflammation, as evidenced by circulating levels of allergen-specific IgE, IgG1, and IgG2a; the profile of inflammatory cells in bronchoalveolar lavage fluid; and the expression of cytokines and mediators in lung tissue. In the systemic model 12/15-LO knockout mice were not protected