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


OBJECTIVE
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.
Hajek
Amanda R
AR
Department of Medicine, Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Lindley
Alexa R
AR
Favoreto
Silvio
S
Carter
Roderick
R
Schleimer
Robert P
RP
Kuperman
Douglas A
DA
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000172:deficiency / Q000378:metabolism*; D001249:Asthma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000097:blood*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012130:Respiratory Hypersensitivity / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
C475064:12-15-lipoxygenase; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase