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Critical role of interleukin-5 in the development of a mite antigen-induced chronic bronchial asthma model

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Abstract

Objective and design

Asthma is associated with eosinophilic airway inflammation and characterized by enhanced airway sensitivity. Interleukin (IL)-5 plays an important role in the pathogenesis of asthma. The involvement of IL-5 receptor-mediated cellular signals in the pathogenesis of a mite antigen-induced chronic asthma model was investigated.

Subjects

In this study, 48 female C57BL/6J (WT) mice and IL-5 receptor-deficient (IL-5RKO) mice were used.

Treatment

Mite antigen (50 μl) was intranasally administered 13 times to WT and IL-5RKO mice.

Methods

Airway hypersensitivity (Mch PC200) and specific antigen exposure tests were performed, and lung tissue, bronchoalveolar lavage fluid (BALF), and blood were collected to investigate the asthma pathology and differences in the local pulmonary levels of cytokines and chemokines.

Results

Airway sensitivity was enhanced and antigen-specific airway resistance was increased in WT mice. In addition, the number of eosinophils and Th2 cytokine levels in the BALF were increased. In contrast, IL-5RKO mice did not acquire the asthma pathology, such as antigen-specific airway resistance and eosinophilic airway inflammation. Mch PC200 was significantly correlated with cysteinyl leukotriene levels in WT mice.

Conclusion

These findings suggested that both IL-5 induced eosinophils and cysteinyl leukotrienes are involved in the pathology of this mite antigen-induced chronic asthma model.

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References

  1. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, Michel F-B. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–9.

    Article  CAS  Google Scholar 

  2. Bousquet JP, Jeffery K, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161:1720–45.

    Article  PubMed  CAS  Google Scholar 

  3. Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000;105:651–63.

    Article  PubMed  CAS  Google Scholar 

  4. Weller PF. Human eosinophils. J Allergy Clin Immunol. 1997;100:283–7.

    Article  PubMed  CAS  Google Scholar 

  5. Piacentini GL, Kaliner MA. The potential roles of leukotrienes in bronchial asthma. Am Rev Respir Dis. 1991;143:S96–9.

    Article  PubMed  CAS  Google Scholar 

  6. Reiss TF, Chervinsky P, Dockhorn RJ, Shingo S, Seidenberg B, Edwards TB, Montelukast Clinical Research Study Group. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Arch Intern Med. 1998;158:1213–20.

    Article  PubMed  CAS  Google Scholar 

  7. Barnes N, Wei LX, Reiss TF, Leff JA, Shingo S, Yu C, Edelman JM. Analysis of montelukast in mild persistent asthmatic patients with near-normal lung function. Respir Med. 2001;95:379–86.

    Article  PubMed  CAS  Google Scholar 

  8. Wardlaw AJ. Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm. J Allergy Clin Immunol. 1999;104:917–26.

    Article  PubMed  CAS  Google Scholar 

  9. Leckie M, ten Brinke JA, Khan J, Diamant Z, O’Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356:2144–8.

    Article  PubMed  CAS  Google Scholar 

  10. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360:985–93.

    Article  PubMed  CAS  Google Scholar 

  11. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;2009(360):973–84.

    Article  Google Scholar 

  12. Katoh S, Fukushima K, Matsumoto N, Matsumoto K, Abe K, Onai N, Matsushima K, Matsukura S. Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy. 2003;58:518–23.

    Article  PubMed  CAS  Google Scholar 

  13. Katoh S, Fukushima K, Matsumoto N, Ehara N, Matsumoto K, Yamauchi A, Hirashima M. Accumulation of CXCR3-expressing eosinophils and increased concentration of its ligands (IP10 and Mig) in bronchoalveolar lavage fluid of patients with chronic eosinophilic pneumonia. Int Arch Allergy Immunol. 2005;137:229–35.

    Article  PubMed  CAS  Google Scholar 

  14. Matsumoto N, Katoh S, Mukae H, Matsuo T, Takatsu K, Matsukura S. Critical role of IL-5 in antigen-induced pulmonary eosinophilia, but not in lymphocyte activation. Arch Allergy Immunol. 2003;130:209–15.

    Article  CAS  Google Scholar 

  15. Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech. 2008;1:213–20.

    Article  PubMed  CAS  Google Scholar 

  16. Katoh S, Kaminuma O, Hiroi T, Mori A, Ohtomo T, Maeda S, Shimizu H, Obase Y, Oka M. CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice. Eur J Immunol. 2011;41:3198–207.

    Article  PubMed  CAS  Google Scholar 

  17. Coffey M, Peters-Golden M. Extending the understanding of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 2003;3:57–63.

    Article  PubMed  CAS  Google Scholar 

  18. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med. 1990;323:645–55.

    Article  PubMed  CAS  Google Scholar 

  19. Tanaka H, Kawada N, Yamada T, Kawada K, Takatsu K, Nagai H. Allergen-induced airway inflammation and bronchial responsiveness in interleukin-5 receptor alpha chain-deficient mice. Clin Exp Allergy. 2000;30:874–81.

    Article  PubMed  CAS  Google Scholar 

  20. Fattouh R, Al-Garawi A, Fattouh M, Arias K, Walker TD, Goncharova S, Coyle AJ, Humbles AA, Jordana M. Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease. Am J Respir Crit Care Med. 2011;183:179–88.

    Article  PubMed  Google Scholar 

  21. Walsh ER, Sahu N, Kearley J, Benjamin E, Kang BH, Humbles A, August A. Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med. 2008;205:1285–92.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Project Research Grants from Kawasaki Medical School, 2012 (23G-5).

Conflict of interest

The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Hiroki Shimizu, Yasushi Obase, Shigeki Katoh, Keiji Mouri, Yoshihiro Kobashi & Mikio Oka

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  1. Hiroki Shimizu
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  2. Yasushi Obase
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  3. Shigeki Katoh
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  4. Keiji Mouri
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  5. Yoshihiro Kobashi
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  6. Mikio Oka
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Corresponding author

Correspondence to Hiroki Shimizu.

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Responsible Editor: Mauro Teixeira.

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Shimizu, H., Obase, Y., Katoh, S. et al. Critical role of interleukin-5 in the development of a mite antigen-induced chronic bronchial asthma model. Inflamm. Res. 62, 911–917 (2013). https://doi.org/10.1007/s00011-013-0651-y

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  • DOI: https://doi.org/10.1007/s00011-013-0651-y

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