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

Amanda R. Hajek, Alexa R. Lindley, Silvio Favoreto, Roderick Carter, Robert P. Schleimer, Douglas A. Kuperman*

*Corresponding author for this work

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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, 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. 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.

Original languageEnglish (US)
Pages (from-to)633-639.e3
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • Asthma
  • B cells
  • IL-13
  • IgA
  • airway
  • allergy
  • inflammation
  • lipoxygenase
  • lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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