Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease

Koichi Waseda, Nobuaki Miyahara, Arihiko Kanehiro, Genyo Ikeda, Hikari Koga, Yasuko Fuchimoto, Etsuko Kurimoto, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Erwin W. Gelfand

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16 Citations (Scopus)

Abstract

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 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. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On 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 through 72. Administration of the antagonist inhibited the secondary ovalbumin challenge-induced alterations in airway responses during the late phase but not during the early phase, as demonstrated by decreases in AHR and in bronchoalveolar lavage neutrophilia and eosinophilia 6 and 48 hours after secondary challenge. The latter was associated with decreased levels of KC protein, macrophage inflammatory protein 2, and IL-17 in the airways. These data identify the importance of the LTB4-BLT1 pathway in the development of late-phase, allergen-induced airway responsiveness after secondary airway challenge in mice with established airway disease.

Original languageEnglish
Pages (from-to)851-857
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number4
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • BLT1 antagonist
  • EAR
  • Established asthma
  • LAR

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Waseda, K., Miyahara, N., Kanehiro, A., Ikeda, G., Koga, H., Fuchimoto, Y., Kurimoto, E., Tanimoto, Y., Kataoka, M., Tanimoto, M., & Gelfand, E. W. (2011). Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease. American journal of respiratory cell and molecular biology, 45(4), 851-857. https://doi.org/10.1165/rcmb.2010-0455OC