Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1, BLT1, have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have already been established, has not been defined.

We investigated the effects of blocking BLT1 on early and late phase development of AHR and airway inflammation in previously sensitized and challenged mice.

Methods: Female BALB/c mice were sensitized (days 1 and 14) and challenged (primary, days 28-30) with ovalbumin (OVA). Six weeks later (day 72), mice were challenged (secondary) with a single OVA aerosol and the early and late phases of AHR and inflammation were determined. Specific blockade of BLT1 was attained by oral administration of a BLT1 antagonist on days 70-72.

Results: Administration of the antagonist inhibited the secondary OVA challenge-induced alterations in airway responses during the late but not early phase, as demonstrated by decreases in AHR, bronchoalveolar lavage (BAL) neutrophilia and eosinophilia 6 and 48 hrs after secondary challenge. The latter was associated with decreased levels of KC, MIP-2, and IL-17 in the airways.

Conclusions: These data identify the importance of the LTB4-BLT1 pathway in the development of late phase allergen-induced airway responsiveness following secondary airway challenge, in mice with established airway disease.

Am J Respir Cell Mol Biol. 2011 Mar 18;
Authors: Waseda K, Miyahara N, Kanehiro A, Ikeda G, Koga H, Fuchimoto Y, Kurimoto E, Tanimoto Y, Kataoka M, Tanimoto M, Gelfand EW
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