Skip to main content
SpringerLink
Log in

Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential influence and the mechanisms leading to differences in strains.

Methods

We applied a mouse model of allergic asthma to BALB/c and C57BL/6 mice.

Results

BALB/c mice displayed greater levels of airway reactivity to methacholine than C57BL/6 mice. Moreover, BALB/c mice exhibited higher numbers of mast cells in lung tissue when compared to C57BL/6. On the contrary, eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) as well as peribronchial eosinophilia were greater in C57BL/6. IL (Interleukin)-4, IL-5, IL-13, and CCL11 levels measured in whole-lung extracts were higher in BALB/c, while, in sharp contrast, CCL11 and CCL5 levels were higher in BALF of C57BL/6 mice.

Conclusions

We observed phenotypic differences between C57BL/6 and BALB/c mice in an asthma model with different distributions of pro-inflammatory cytokines and inflammatory cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Hellings PW, Ceuppens JL. Mouse models of global airway allergy: what have we learned and what should we do next? Clin Exp Allergy. 2004;59:914–9.

    CAS  Google Scholar 

  2. Fan T, Yang M, Halayko A, Mohapatra SS, Stephens NL. Airway responsiveness in two inbred strains of mouse disparate in IgE and IL-4 production. Am J Respir Cell Mol Biol. 1997;17:156–63.

    CAS  PubMed  Google Scholar 

  3. Tournoy KG, Hove C, Grooten J, Moerloose K, Brusselle GG, Joos GF. Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma? Clin Exp Allergy. 2006;36:8–20.

    Article  CAS  PubMed  Google Scholar 

  4. Crimi E, Spanevello A, Neri M, Ind PW, Rossi GA, Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med. 1998;157(1):4–9.

    CAS  PubMed  Google Scholar 

  5. Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanovic R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000;161:9–16.

    CAS  PubMed  Google Scholar 

  6. Oddera S, Silvestri M, Penna R, Galeazzi G, Crimi E, Rossi GA. Airway eosinophilic inflammation and bronchial hyperresponsiveness after allergen inhalation challenge in asthma. Lung. 1998;176:237–47.

    Article  CAS  PubMed  Google Scholar 

  7. De Sanctis GT, Daheshia M, Daser A. Genetics of airway hyperresponsiveness. J Allergy Clin Immunol. 2001;108:11–20.

    Article  PubMed  Google Scholar 

  8. Takeda K, Haczku A, Lee JJ, Irvin CG, Gelfand EW. Strain dependence of airway hyperresponsiveness reflects differences in eosinophil localization in the lung. Am J Physiol Lung Cell Mol Physiol. 2001;281:394–402.

    Google Scholar 

  9. Wills-Karp M, Ewart SL. The genetics of allergen-induced airway hyperresponsiveness in mice. Am J Respir Crit Care Med. 1997;156:89–96.

    Google Scholar 

  10. Shinagawa K, Kojima M. Mouse model of airway remodeling: strain differences. Am J Respir Crit Care Med. 2003;168:959–67.

    Article  PubMed  Google Scholar 

  11. Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med. 1997;156:766–75.

    CAS  PubMed  Google Scholar 

  12. Hantos Z, Collins RA, Turner DJ, Janosi TZ, Sly PD. Tracking of airway and tissue mechanics during TLC maneuvers in mice. J Appl Physiol. 2003;95:1695–705.

    PubMed  Google Scholar 

  13. Cataldo DD, Tournoy KG, Vermaelen K, Munaut C, Foidart JM, Louis R, et al. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation. Am J Pathol. 2002;161:491–8.

    CAS  PubMed  Google Scholar 

  14. Gueders MM, Balbin M, Rocks N, Foidart JM, Gosset P, Louis R, et al. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J Immunol. 2005;175:2589–97.

    CAS  PubMed  Google Scholar 

  15. Gueders MM, Bertholet P, Perin F, Rocks N, Maree R, Botta V, et al. A novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma. Biochem Pharmacol. 2008;75:514–26.

    Article  CAS  PubMed  Google Scholar 

  16. Louis R, Sele J, Henket M, Cataldo D, Bettiol J, Seiden L, et al. Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness. Allergy. 2002;57:907–12.

    Article  CAS  PubMed  Google Scholar 

  17. Flandre TD, Leroy PL, Desmecht DJ. Effect of somatic growth, strain, and sex on double-chamber plethysmographic respiratory function values in healthy mice. J Appl Physiol. 2003;94:1129–36.

    PubMed  Google Scholar 

  18. Leigh R, Ellis R, Wattie JN, Hirota JA, Matthaei KI, Foster PS, et al. Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice. Am J Respir Crit Care Med. 2004;169:860–7.

    Article  PubMed  Google Scholar 

  19. Yang G, Volk A, Petley T, Emmell E, Giles-Komar J, Shang X, et al. Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodelling. Cytokine. 2004;28:224–32.

    Article  CAS  PubMed  Google Scholar 

  20. Yang G, Li L, Volk A, Emmell E, Petley T, Giles-Komar J, et al. Therapeutic dosing with anti-interleukin-13 monoclonal antibody inhibits asthma progression in mice. J Pharmacol Exp Ther. 2005;313:8–15.

    Article  CAS  PubMed  Google Scholar 

  21. Eum SY, Maghni K, Tolloczko B, Eidelman DH, Martin JG. IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2005;288:576–84.

    Article  Google Scholar 

  22. Jeffery PK, Haahtela T. Allergic rhinitis and asthma: inflammation in a one-airway condition. BMC Pulm Med. 2006;6:1–5.

    Article  Google Scholar 

  23. Bradding P, Walls AF, Holgate ST. The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol. 2006;117:1277–84.

    Article  CAS  PubMed  Google Scholar 

  24. Nakae S, Lunderius C, Ho LH, Schäfer B, Tsai M, Galli SJ. TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice. J Allergy Clin Immunol. 2007;119:680–6.

    Article  CAS  PubMed  Google Scholar 

  25. Kim YS, Ko HM, Kang NI, Song CH, Zhang X, Chung WC, et al. Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-alpha in a murine model of asthma. Eur J Immunol. 2007;37:1107–15.

    Article  CAS  PubMed  Google Scholar 

  26. Brightling CE, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID, Bradding P. Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma. Clin Exp Allergy. 2003;33:1711–6.

    Article  CAS  PubMed  Google Scholar 

  27. Ichinose T, Takano H, Sadakane K, Yanagisawa R, Yoshikawa T, Sagai M, et al. Mouse strain differences in eosinophilic airway inflammation caused by intratracheal instillation of mite allergen and diesel exhaust particles. J Appl Toxicol. 2004;24:69–76.

    Article  CAS  PubMed  Google Scholar 

  28. Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR. Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol. 1999;162:2477–87.

    CAS  PubMed  Google Scholar 

  29. Rojas-Ramos E, Avalos AF, Perez-Fernandez L, Cuevas-Schacht F, Valencia-Maqueda E, Teran LM. Role of the chemokines RANTES monocyte chemotactic proteins-3 and -4, and eotaxins-1 and -2 in childhood asthma. Eur Respir J. 2003;22:310–6.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Y, Lamm WJ, Albert RK, Chi EY, Henderson WR, Lewis DB. Influence of the route of allergen administration and genetic background on the murine allergic pulmonary response. Am J Respir Crit Care Med. 1997;155:661–9.

    CAS  PubMed  Google Scholar 

  31. Coffman RL, Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986;136:949–54.

    CAS  PubMed  Google Scholar 

  32. Keen JC, Sholl L, Wills-Karp M, Georas SN. Preferential activation of nuclear factor of activated T cells c correlates with mouse strain susceptibility to allergic responses and interleukin-4 gene expression. Am J Respir Cell Mol Biol. 2001;24:58–65.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants of the Walloon Region Government (DGTRE), the Fonds National de la Recherche Scientifique (FNRS, Brussels, Belgium), the Fondation Leon Fredericq (University of Liege), the CHU (Liege, Belgium), Action de Recherches Concertées, Communauté Française de Belgique and European Union (FP6), the Interuniversity Attraction Poles Programme—Belgian Science Policy (Brussels, Belgium). D.C. is a research associate of the FNRS. N.R. and G.P. received grants from the Télévie and FRIA (FNRS, Belgium), respectively. The authors are indebted to Fabienne Perin, Christine Fink, and Fabrice Olivier for their excellent technical assistance.

Author information

Authors and Affiliations

  1. Department of Tumors and Developmental Biology, GIGA-Research (GIGA-I³ and GIGA-Cancer), University of Liege and CHU of Liege, Tower of Pathology B23, 4000, Liege, Belgium

    Maud M. Gueders, Genevieve Paulissen, Celine Crahay, Florence Quesada-Calvo, Jonathan Hacha, Jean-Michel Foidart, Agnes Noël & Didier D. Cataldo

  2. Department of Respiratory Diseases, GIGA-Research (GIGA-I³ and GIGA-Cancer), University of Liege and CHU of Liege, Liege, Belgium

    Maud M. Gueders, Renaud Louis & Didier D. Cataldo

  3. Department of Respiratory Medicine, Ghent University, Ghent, Belgium

    Chris Van Hove & Kurt Tournoy

Authors
  1. Maud M. Gueders
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Genevieve Paulissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Celine Crahay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florence Quesada-Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonathan Hacha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chris Van Hove
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kurt Tournoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Renaud Louis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean-Michel Foidart
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Agnes Noël
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Didier D. Cataldo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Didier D. Cataldo.

Additional information

Responsible Editor: M. Parnham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gueders, M.M., Paulissen, G., Crahay, C. et al. Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production. Inflamm. Res. 58, 845–854 (2009). https://doi.org/10.1007/s00011-009-0054-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-009-0054-2

Keywords

Search

Navigation