Role of prostaglandin D2 receptor CRTH2 in sustained eosinophil accumulation in the airways of mice with chronic asthma

Shizuko Kagawa, Koichi Fukunaga, Tsuyoshi Oguma, Yusuke Suzuki, Tetsuya Shiomi, Koichi Sayama, Tokuhiro Kimura, Hiroyuki Hirai, Kinya Nagata, Masataka Nakamura, Koichiro Asano

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Abstract

The prostaglandin D2 (PGD2)/CRTH2 pathway is important for eosinophil trafficking in vitro; however, genetic deficiency of CRTH2 does not suppress in vivo eosinophilic airway inflammation in acute models of asthma, and the role of CRTH2 in the pathogenesis of asthma is still ambiguous. Therefore, in the present study we explored whether the PGD 2/CRTH2 pathway could affect the phenotypes of chronic asthma. Either CRTH2-deficient (CRTH2-/-) or wild-type mice were sensitized and exposed to ovalbumin (OVA) for 3 days (acute model) or 6 weeks (chronic model). While the magnitude of the acute eosinophilic inflammation was equivalent between CRTH2-/- and wild-type mice, the number of inflammatory cells and eosinophils in bronchoalveolar lavage fluid after chronic OVA exposure was significantly reduced in CRTH2-/- mice (18.0 ± 2.6 × 104 cells and 2.0 ± 0.5 × 104 cells) compared to wild-type mice (27.9 ± 2.5 × 104 cells and 6.8 ± 1.1 × 10 4 cells, p < 0.001). On the contrary, no difference was observed between CRTH2-/- and wild-type mice in terms of airway hyperresponsiveness or remodeling (goblet cell hyperplasia) in the chronic model of asthma. In conclusion, CRTH2 that mediates PGD2 activity is essential for sustained eosinophilic inflammation in the airways, and its antagonists could exert an anti-inflammatory effect in chronic asthma.

Original languageEnglish
Pages (from-to)6-11
Number of pages6
JournalInternational Archives of Allergy and Immunology
Volume155
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2011 Jun 1

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Keywords

  • Airway responsiveness, remodeling
  • Eosinophils
  • Lung
  • Mucus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kagawa, S., Fukunaga, K., Oguma, T., Suzuki, Y., Shiomi, T., Sayama, K., Kimura, T., Hirai, H., Nagata, K., Nakamura, M., & Asano, K. (2011). Role of prostaglandin D2 receptor CRTH2 in sustained eosinophil accumulation in the airways of mice with chronic asthma. International Archives of Allergy and Immunology, 155(SUPPL. 1), 6-11. https://doi.org/10.1159/000327257