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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:122

Article

Hajek, Amanda R.¹  Lindley, Alexa R.¹  Favoreto, Silvio, Jr.¹  Carter, Roderick¹  Schleimer, Robert P.¹  Kuperman, Douglas A.¹ 

[1] Northwestern Univ, Feinberg Sch Med, Div Allergy Immunol, Dept Med, Chicago, IL 60611 USA

关键词: asthma;    allergy;    inflammation;    lipoxygenase;    IL-13;    IgA;    B cells;    airway;    lung;   

DOI  :  10.1016/j.jaci.2008.06.021

来源: Elsevier

【 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-1 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, lgG1, 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. This suggested the presence of a lung-restricted protective role for 12/15-LO deficiency that was potentially accounted for by increased activation of mucosal B cells and increased production of the known mucosal-specific protective mediator secretory IgA. Conclusions: Induction of 15-LO-1 in asthma might contribute to allergic sensitization and airways inflammation, potentially by causing suppression of secretory IgA.

【 授权许可】

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