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

J Allergy Clin Immunol. 2008 Sep;122(3):633-9.e3. doi: 10.1016/j.jaci.2008.06.021. Epub 2008 Aug 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / deficiency
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Arachidonate 15-Lipoxygenase / deficiency
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Asthma / enzymology
  • Asthma / immunology*
  • Asthma / pathology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Immunoglobulin A, Secretory / blood*
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lung / immunology*
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Respiratory Hypersensitivity / enzymology
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology


  • 12-15-lipoxygenase
  • Cytokines
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Immunoglobulin E
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase