Inflammation Research

, 58:773 | Cite as

Intranasal challenge with increasing ovalbumin doses differently affects airway hyperresponsiveness and inflammatory cell accumulation in mouse model of asthma

  • Berislav Bošnjak
  • Vanesa Ivetić Tkalčević
  • Koraljka Đurić
  • Daniela Belamarić
  • Snježana Čužić
  • Željko Ferenčić
  • Karmen Brajša
  • Ines Glojnarić
  • Roberto Antolović
  • Boška Hrvačić
Original Research Paper

Abstract

Objective

To investigate whether challenge with increasing allergen doses could differently affect allergen-induced airway hyperresponsiveness (AHR) and inflammatory cell accumulation in mouse model of asthma, providing an experimental model to investigate their relationship.

Material and methods

AHR and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and into the lungs were compared in ovalbumin-sensitized mice that were challenged intranasally with 2.5, 10, 25 or 100 μg of ovalbumin/mouse.

Results

Both AHR and inflammatory cell accumulation were proportional to the ovalbumin dose used for challenge. However, in group challenged with 10 μg of ovalbumin airway inflammation was present, although allergen-induced AHR was not detected. Additional analysis indicated that neither mucous hyperproduction nor eosinophil degranulation could be correlated to presence of AHR in this model, whereas concentration of interleukin (IL)-13 in BALF was increased only in those groups in which AHR was present.

Conclusions

Altogether, intranasal challenge of mice with increasing allergen doses could serve as a suitable experimental system for investigation of mechanisms by which airway inflammation leads to allergen-induced AHR. Our initial findings are in line with previous reports that dissociate AHR from amount of eosinophil accumulation and imply the role of IL-13 in this process.

Keywords

Airway hyperresponsiveness Allergen dose Asthma Eosinophils Mice 

Abbreviations

AHR

Airway hyperresponsiveness

BALF

Bronchoalveolar lavage fluid

EPO

Eosinophil peroxidase

IL

Interleukin

PAS

Periodic acid-Schiff

SEM

Standard error of the mean

References

  1. 1.
    Bousquet J, Jeffery PK, Busse WW, Johnson M, Vingola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161:1720–45.PubMedGoogle Scholar
  2. 2.
    Canonica GW. Treating asthma as an inflammatory disease. Chest. 2006;130:21S–8S.PubMedCrossRefGoogle Scholar
  3. 3.
    Cockcroft DW, Murdock KY. Changes in bronchial responsiveness to histamine at intervals after allergen challenge. Thorax. 1987;42:302–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Durham SR, Craggock CF, Cookson WO, Benson MK. Increases in airway responsiveness to histamine precede allergen-induced late asthmatic responses. J Allergy Clin Immunol. 1988;82:764–70.PubMedCrossRefGoogle Scholar
  5. 5.
    O’Byrne PM, Inman MD. Airway hyperresponsiveness. Chest. 2003;123:411S–6S.PubMedCrossRefGoogle Scholar
  6. 6.
    Cockroft DW, Davis BE. Mechanisms of airway hyperresponsiveness. J Allergy Clin Immunol. 2006;118:551–9.CrossRefGoogle Scholar
  7. 7.
    Venkayya R, Lam M, Willkom M, Grunig G, Corry DB, Erle DJ. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am J Respir Cell Mol Biol. 2002;26:202–8.PubMedGoogle Scholar
  8. 8.
    Proust B, Nahori MA, Ruffie C, Lefort J, Vargaftig BB. Presence of bronchopulmonary hyper-reactivity and eosinophilic lung inflammation after anti-IL-5 or -IL-13 treatment in allergic BALB/c and IL-4Ralpha knockout mice. Clin Exp Allergy. 2003;33:119–31.PubMedCrossRefGoogle Scholar
  9. 9.
    Lai CKW, Twentyman OP, Holgate ST. The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and associated challenges in nonspecific bronchial responsiveness. Am Rev Respir Dis. 1989;140:917–23.PubMedGoogle Scholar
  10. 10.
    Frolund L, Madsen F, Scharling B, Heinig JH, Gerner Svendsen U. Bronchial allergen challenge: dose versus concentration. Clin Exp Allergy. 1992;22:219–25.PubMedCrossRefGoogle Scholar
  11. 11.
    Boulet L-P, Gauvreau G, Boulay M-E, O’Byrne P, Cockcroft DW. The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti-inflammatory therapies. Allergy. 2007;67:1101–10.CrossRefGoogle Scholar
  12. 12.
    Dupuis R, Collins DS, Koh YY, Pollice M, Albertine KH, Fish JE, et al. Effect of antigen dose on the recruitment of inflammatory cells to the lung by segmental antigen challenge. J Allergy Clin Immunol. 1992;89:850–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Jarjour NN, Calhoun WJ, Kelly EA, Gleich GJ, Schwartz LB, Busse WW. The immediate and late allergic response to segmental bronchopulmonary provocation in asthma. Am J Respir Crit Care Med. 1997;155:1515–21.PubMedGoogle Scholar
  14. 14.
    Platts-Mills TEA, Sporik RB, Wheatley LM, Heymann PW. Is there a dose–response relationship between exposure to indoor allergens and symptoms of asthma? J Allergy Clin Immunol. 1995;96:435–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Epstein MM. Do mouse models of allergic asthma mimic clinical disease? Int Arch Allergy Immunol. 2004;133:84–100.PubMedCrossRefGoogle Scholar
  16. 16.
    Zosky GR, Larcombe AN, White OJ, Burchell JT, Janosi TZ, Hantos Z, et al. Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation. Clin Exp Allergy. 2008;38:829–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Irvin CG. Using the mouse to model asthma: the cup is half full and then some. Clin Exp Allergy. 2008;38:701–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Tomkinson A, Cieslewicz G, Duez C, Larson KA, Lee JJ, Gelfand EW. Temporal association between airway hyperresponsiveness and airway eosinophilia in ovalbumin-sensitized mice. Am J Respir Crit Care Med. 2001;163:721–30.PubMedGoogle Scholar
  19. 19.
    Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethismography. Am J Respir Crit Care Med. 1997;156:766–75.PubMedGoogle Scholar
  20. 20.
    Strath M, Warren DJ, Sanderson CJ. Detection of eosinophils using an eosinophil peroxidase assay: its use as an assay for eosinophil differentiation factors. J Immunol Methods. 1985;83:209–15.PubMedCrossRefGoogle Scholar
  21. 21.
    Pretolani M, Ruffie C, Joseph D, Campos MG, Church MK, Lefort J, et al. Role of eosinophil activation in the bronchial reactivity of allergic guinea pigs. Am J Respir Crit Care Med. 1994;149:1167–74.PubMedGoogle Scholar
  22. 22.
    Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.PubMedCrossRefGoogle Scholar
  23. 23.
    Dabbagh K, Takeyama K, Lee HM, Ueki IK, Lausier JA, Nadel JA. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol. 1999;162:6233–7.PubMedGoogle Scholar
  24. 24.
    Chung YJ, Coates NH, Viana ME, Copeland L, Vesper SJ, Selgrade MK, et al. Dose-dependent allergic responses to an extract of Penicillium chrysogenum in BALB/c mice. Toxicology. 2005;209:77–89.PubMedCrossRefGoogle Scholar
  25. 25.
    Arts JHE, de Koning MW, Bloksma N, Kuper CF. Respiratory allergy to trimellitic anhydride in rats: concentration–response relationships during elicitation. Inhal Toxicol. 2004;16:259–69.PubMedCrossRefGoogle Scholar
  26. 26.
    Taube C, Nick JA, Siegmund B, Duez C, Takeda K, Rha YH, et al. Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. Am J Respir Cell Mol Biol. 2004;30:837–43.PubMedCrossRefGoogle Scholar
  27. 27.
    Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, et al. A critical role for eosinophils in allergic airways remodeling. Science. 2004;305:1776–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Hessel EM, Van Oosterhout AJ, Van Ark I, Van Esch B, Hofman G, Van Loveren H, et al. Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration. Am J Respir Cell Mol Biol. 1997;16:325–34.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Berislav Bošnjak
    • 1
    • 2
  • Vanesa Ivetić Tkalčević
    • 1
  • Koraljka Đurić
    • 1
    • 3
  • Daniela Belamarić
    • 1
  • Snježana Čužić
    • 1
  • Željko Ferenčić
    • 1
    • 4
  • Karmen Brajša
    • 1
  • Ines Glojnarić
    • 1
  • Roberto Antolović
    • 1
  • Boška Hrvačić
    • 1
  1. 1.GlaxoSmithKline Research Centre Zagreb LimitedZagrebCroatia
  2. 2.Experimental Allergy, Division of Immunology, Allergy and Infectious Diseases, Department of DermatologyMedical University of ViennaViennaAustria
  3. 3.Medical Biochemistry LaboratoryPoliclinic SunceZagrebCroatia
  4. 4.Children’s Hospital SREBRNJAKZagrebCroatia

Personalised recommendations