Mice Lacking 12/15-Lipoxygenase have Attenuated Airway Allergic Inflammation and Remodeling.

Cecilia Andersson, Hans-Erik Claesson, Kristina Rydell-Törmänen, Stellan Swedmark, Anneli Hallgren, Jonas Erjefält

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes (eosinophils, lymphocytes macrophages) and Th2 cytokines (IL-4, IL-5, IL-13) as well as tissue eosinophils. Allergen-induced airway epithelial proliferation was also significantly attenuated in 12/15 LO(-/-) mice whereas goblet cell hyperplasia was unaffected. However, 12/15 LO(-/-) mice had significantly reduced luminal mucus secretions compared to Wt controls. The repeated allergen challenges resulted in a dramatic increase of alpha-smooth muscle-actin positive alveolar cells in the peripheral airways, a phenomenon that was significantly less developed in 12/15 LO(-/-) mice. In conclusion, our data suggest that 12/15 LO(-/-) mice, although having a fully developed systemic sensitization, did not establish a fully developed allergic airway inflammation and associated manifestations of central and peripheral airway remodeling. These data suggest that 12/15-LO derived metabolites play an important pathophysiological role in allergen-induced inflammation and remodeling. Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma.
Sidor (från-till)648-656
Antal sidor9
TidskriftAmerican Journal of Respiratory Cell and Molecular Biology
StatusPublished - 2008 dec.

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi


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