Skip to main content

Animal Models of Experimental Asthma

  • Conference paper
Animal Models of T Cell-Mediated Skin Diseases

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 50))

4.5 Conclusions

Animal models which mimic the hallmarks of human bronchial asthma are urgently needed. Such models provide important insight into the pathophysiology of the disease. However, the phenotype of such models must be carefully assessed. Most of the models currently available reflect the stage of acute asthmatic responses with airway inflammation, airway hyperresponsiveness, and sometimes mucus production. However, bronchial asthma represents a chronic disease with chronic and persistent airway inflammation, involvement of the smaller airways, structural changes within and beneath mucosal tissues, and persistent airway obstruction. Advances have been made in further developing models which mimic this phenotype much more closely. These models are particularly relevant in terms of developing novel therapeutic approaches for immuno-intervention in this complex disease. In the future it will be necessary to develop preventive strategies as well as strategies which specifically and sufficiently interfere in structural changes of the airways, since none of the currently available therapies are able to prevent or stop the beginning of airway remodeling.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alarie Y (1966) Irritating properties of airborne materials to the upper respiratory tract. Arch Environ Health 13:433–449

    PubMed  CAS  Google Scholar 

  • Ambdur M, Mead J (1958) Mechanics of respiration in unanesthetized guinea-pigs. Am J Physiol 192:364–368

    Google Scholar 

  • Beasley R, Roche WR, Roberts JA, et al (1989) Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis 139:806–817

    PubMed  CAS  Google Scholar 

  • Boggs D (1992) Comparative control of respiration. In Parent RA, Comparative biology of the normal lung. CRC Press, Boca Raton, pp 309–351

    Google Scholar 

  • Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al (1990) Eosinophilic inflammation in asthma. N Engl J Med 323:1033–1039

    PubMed  CAS  Google Scholar 

  • Bradding P (1996) Human mast cell cytokines. Clin Exp Allergy 26:13–19

    Article  PubMed  CAS  Google Scholar 

  • Braun A, Lommatzsch M, Mannsfeldt A, Neuhaus-Steinmetz U, Fischer A, Schnoy N, Lewin GR, Renz H (1999) Cellular sources of enhanced brain-derived neurotrophic factor (BDNF) production in a mouse model of allergic inflammation. Am J Respir Cell Mol Biol 21:537–546

    PubMed  CAS  Google Scholar 

  • von Bubnoff D, Novak N, Kraft S, Bieber T (2003) The central role of FcÉ›RI in allergy. Clin Exp Dermatol 28:184–187

    Article  Google Scholar 

  • Busse WW, Sedgwick JB (1994) Eosinophil eicosanoid relations in allergic inflammation of the airways. Adv Prostaglandin Thromboxane Leukot Res 22:241–249

    PubMed  CAS  Google Scholar 

  • Clutterbuck EJ, Sanderson CJ (1998) Human eosinophil hematopiesis studied in vitro by means of murine eosinophil differentiation factor (IL-5): production of functionally active eosinophils from normal human bone marrow. BMJ 71:646–651

    Google Scholar 

  • Collins DS, Dupuis GJ, Gleich KR, Bartemes KR, Koh YY, Pollice M, Albertine KH, Fish JE, Peters SP (1993) Immunoglobulin E-mediated increase in vascular permeability correlates with eosinophilic inflammation. Am Rev Respir Dis 147:677–683

    PubMed  CAS  Google Scholar 

  • Cookson W (1999) The alliance of genes and environment in asthma and allergy. Nature 402:B5–11

    Article  PubMed  CAS  Google Scholar 

  • Corrigan CJ, Kay AB (1992) T cells and eosinophils in the pathogenesis of asthma. Immunol Today 13:501–507

    Article  PubMed  CAS  Google Scholar 

  • Corry DB, Grunig G, Hadeiba H, Kurup VP, Warnock ML, Sheppard D, et al (1998) Requirements for allergen-induced airway hyperreactivity in T and B cell-deficient mice. Mol Med 4:344–355

    Article  PubMed  CAS  Google Scholar 

  • Drazen JM, Arm JP, Austen KF (1996) Sorting out the cytokines of asthma. J Exp Med 183:1–5

    Article  PubMed  CAS  Google Scholar 

  • Eckert R, Randall D (1988) Animal physiology-mechanisms and adaptions. WH Freeman and Company, San Francisco, pp 68–84

    Google Scholar 

  • Ellis JL, Hubbard WC, Meeker S, et al (1994) Ragweed antigen E and anti-IgE in human central versus peripheral isolated bronchi. Am J Respir Crit Care Med 150:717–723

    PubMed  CAS  Google Scholar 

  • Finotto S, De Sanctis GT, Lehr HA, Herz U, Buerke M, Schipp M, Bartsch B, Atreya R, Schmitt E, Galle PR, Renz H, Neurath MF (2001) Treatment of allergic airway inflammation and hyperresponsiveness by antisense-in-duced local blockade of GATA-3 expression. J Exp Med 193:1247–1260

    Article  PubMed  CAS  Google Scholar 

  • Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, Barnes N, Robinson D, Kay AB (2003) Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 112(7):1029–1036

    PubMed  CAS  Google Scholar 

  • Foster H (1983) The mouse in biomedical research, Vol III. Academic Press

    Google Scholar 

  • Foster PS, Hogan SP, Ramsay EJ, Matthaei KI, Young IG (1996) Interleu-kin-5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 183:195–201

    Article  PubMed  CAS  Google Scholar 

  • Gavett SH, Chen X, Finkelman F, Wills-Karp M (1994) Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol 10:587–593

    PubMed  CAS  Google Scholar 

  • Glaab T, Daser A, Braun Steinmetz-Neuhaus U, Fabel H, Alarie Y, Renz H (2001) Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice. Am J Physiol Lung Cell Mol 280:L565–573

    CAS  Google Scholar 

  • Gleich GJ, Adolphson CR, Leiferman KM (1993) The biology of the eosinophilic leukocyte. Annu Rev Med 44:85–101

    Article  PubMed  CAS  Google Scholar 

  • Haley KJ, Sunday ME, Wiggs BR, Kozakewich HP, Reilly JJ, Mentzer SJ, Sugarbaker DJ, Doerschuk CM, Drazen JM (1998) Inflammatory cell distribution within and along asthmatic airways. Am J Respir Crit Care Med 158:565–572

    PubMed  CAS  Google Scholar 

  • Hamelmann E, et al (1997) Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 156:766–775

    PubMed  CAS  Google Scholar 

  • Hegele RG, Hogg JC (1996) The pathology of asthma: an inflammatory disorder. In: Szefler SJ, Leung DYM (eds) Severe asthma: pathogenesis and clinical management. Marcel Dekker, New York, pp 61–76

    Google Scholar 

  • Hertz M, Mahalingam S, Dalum I, Klysner S, Mattes J, Neisig A, Mouritsen S, Foster PJ, Gautam A (2001) Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma. J Immunol 167:3792–3799

    PubMed  CAS  Google Scholar 

  • Hogan SP, Mould A, Kikutani H, Ramsay AJ, Foster PS (1997) Aeroaller-gen-induced eosinophilic inflammation, lung damage, and airways hyperreactivity in mice can occur independently of IL-4 and allergen-specific immunoglobulins. J Clin Invest 99:1329–1339

    Article  PubMed  CAS  Google Scholar 

  • Hogan SP, Koskinen A, Matthaei KI, Young IG, Foster PS (1998a) Interleu-kin-5-producing CD4+ T cells play a pivotal role in aeroallergen-induced eosinophilia, bronchial hyperreactivity, and lung damage in mice. Am J Respir Crit Care Med 157:210–218

    PubMed  CAS  Google Scholar 

  • Hogan SP, Mathtaei KI, Young JM, Koskinen A, Young IG, Foster PS (1998b) A novel T cell-regulated mechanism modulating allergen-induced hyperreactivity in BLAB/c mice independently of IL-4 and IL-5. J Immunol 161:1501–1509

    PubMed  CAS  Google Scholar 

  • Hogg JC (1993) The pathology of asthma. In: Holgate ST, Austen KF, Lich-tenstein LM, et al (eds) Asthma: physiology, immunopharmacology and treatment. Academic Press, London, pp 17–25

    Google Scholar 

  • Holz O, Jorres RA, Magnussen H (2000) Monitoring central and peripheral airway inflammation in asthma. Respir Med 94:S7–12

    PubMed  Google Scholar 

  • Izuhara K, Arima K, Yasunaga S (2002) IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies. Curr Drug Targets Inflamm Allergy 1:263–269

    Article  PubMed  CAS  Google Scholar 

  • James AL, Pare PD, Hogg JC (1989) The mechanics of airway narrowing in asthma. Am Rev Respir Dis 139:242–246

    PubMed  CAS  Google Scholar 

  • Kaminuma O, Mori A, Ogawa K, Nakata A, Kikkawa H, Naito K, Suko M, Okudaira H (1997) Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones. Am J Respir Cell Mol Bid 16:448–454

    CAS  Google Scholar 

  • Kanehiro A, Ikemura T, Makela MJ, Lahn M, Joetham A, Dakhama A, Gelfand EW (2001) Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. Am J Respir Crit Care Med 163:173–184

    PubMed  CAS  Google Scholar 

  • Kenyon NJ, Ward RW, Last JA (2003) Airway fibrosis in a mouse model of airway inflammation. Toxicol Appl Pharmacol 186:90–100

    Article  PubMed  CAS  Google Scholar 

  • Kerzel S, Päth G, Nockher WA, Quarcoo D, Raap U, Groneberg DA, Thai Dinh Q, Fischer A, Braun A, Renz H (2003) Pan-Neurotrophin Receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol 28:170–178

    Article  PubMed  CAS  Google Scholar 

  • Kinet JP (1990) The high-affinity receptor for immunoglobulin E. Curr Opin Immunol 2:499–505

    Article  CAS  Google Scholar 

  • Korsgren M, Erjefalt JS, Korsgren O, Sundler F, Persson CG (1997) Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice. J Exp Med 185:885–892

    Article  PubMed  CAS  Google Scholar 

  • Kraft M (1999) The distal airways: are they important in asthma? Eur Respir J 14:1403–1417

    Article  PubMed  CAS  Google Scholar 

  • Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, et al (1997) Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomic of asthma. J Exp Med 185:2143–2156

    Article  PubMed  CAS  Google Scholar 

  • Leff AR (1994) Inflammatory mediation of airway hyperresponsiveness by peripheral blood granulocytes: the case for the eosinophil. Chest 106:1202–1208

    Article  PubMed  CAS  Google Scholar 

  • Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA (1988) Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 167:219–224

    Article  PubMed  CAS  Google Scholar 

  • Lungarella G, Menegazzi R, Gardi C, Spessotto M, de Santi M, Bertocin P, Patriarca P, Calzoni P Zabucchi G (1992) Identification of elastase in human eosinophils: immunolocalization, isolation, and partial characterization. Arch Biochem Biophys 292:128–135

    Article  PubMed  CAS  Google Scholar 

  • Marthur M, Herrmann K, Li X, Qin Y, Weinstock J, Elliott D, et al (1999) TRFK-5 reverses established airway eosinophilia but not established hyperresponsiveness in a murine model of chronic asthma. Am J Respir Crit Care Med 159:580–587

    Google Scholar 

  • Neuhaus-Steinmetz U, Glaab T, Daser A, Braun A, Lommatzsch M, Herz U, Kips J, Alarie Y, Renz H. (2000) Sequential development of airway hyperresponsiveness and acute airway obstruction in a mouse model of allergic inflammation. Int Arch Allergy Immunol 121(l):57–67

    Article  PubMed  CAS  Google Scholar 

  • Oh SW, Pae CI, Lee DK, Jones F, Chiang GK, Kim HO, Moon SH, Cao B, Ogbu C, Jeong KW, Kozu G, Nakanishi H, Kahn M, Chi EY, Henderson WR (2002) Tryptase inhibition blocks airway inflammation in a mouse asthma model. J Immunol 168:1992–2000

    PubMed  CAS  Google Scholar 

  • Ohno I, Lea RG, Flanders KC, Clark DA, Banwatt D, Dolovich J, Denburg J, Harley CB, Gauldie J, Jordana M (1992) Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest 89:1662–1668

    Article  PubMed  CAS  Google Scholar 

  • Palmans E, Kips JC, Pauwels RA (2000) Prolonged allergen exposure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med 161:627–635

    PubMed  CAS  Google Scholar 

  • Päth G, Braun A, Meents N, Kerzel S, Raap U, Hoyle GW, Nockher WA, Renz H (2002) Augmentation of allergic early-phase reaction by Nerve Growth Factor (NGF). Am J Respir Crit Care Med 166:818–826

    Article  PubMed  Google Scholar 

  • Rabe KF, Munoz NM, Vita AJ, Morton BE, Magnussen H, Leff AR (1994) Contraction of human bronchial smooth muscle caused by activated human eosinophils. Am J Physiol 267:L326–334

    PubMed  CAS  Google Scholar 

  • Renz H, Smith HR, Henson JE, Ray BS, Irvin CG, Gelfand EW (1992) Aerosolized antigen exposure without adjuvant causes increased IgE production and airways hyperresponsiveness in the mouse. J All Clin Immunol 89:1127–1138

    Article  CAS  Google Scholar 

  • Renz H, Or R, Domenico J, Leung DYM, Gelfand EW (1992) Reciprocal regulatory effects of IL-4 on cell growth and immunoglobulin production in Ig-secreting human B-cell lines. Clin Immunol Immunopathol 64:233–241

    Article  PubMed  CAS  Google Scholar 

  • Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB (1992) Predominant TH2-like broncho-alveolar T-lymphocyte population in atopic asthma. N Engl J Med 326: 298–304

    PubMed  CAS  Google Scholar 

  • Sakai K, Yokohama A, Kouno N, Hamada H, Hiwada K (2001) Prolonged antigen exposure ameliorates airway inflammation but not remodelling in a mouse model of bronchial asthma. Int Arch Allergy Immunol 126:126–134

    Article  PubMed  CAS  Google Scholar 

  • Sanderson CJ (1988) Interleukin-5: an eosinophil growth and activation factor. Dev Biol Stand 69:23–29

    PubMed  CAS  Google Scholar 

  • Sanderson CJ (1990) The biological role of interleukin 5. Int J Cell Cloning 8:147–153

    Article  PubMed  CAS  Google Scholar 

  • Shi HZ, Xiao CQ, Zhong D, Qin SM, Liu Y, Liang GR, Xu H, Chen YQ, Long XM, Xie ZF (1998) Effect of inhaled interleukin-5 on airway hyperreactivity and eosinophilia in asthmatics. Am J Respir Crit Care Med 157:204–209

    PubMed  CAS  Google Scholar 

  • Shi HZ, Humbles A, Gerard C, Jin Z, Weller PF (2000) Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest 105:945–953

    Article  PubMed  CAS  Google Scholar 

  • Temelkowski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK (1998) An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax 53:849–856

    Article  Google Scholar 

  • Vignola AM, Chanez P, Campbell AM, Souques F, Lebel B, Enander I, Bousquet J (1998) Airway inflammation in mild intermittent and in persistent asthma. Am J Respir Crit Care Med 157:403–440

    PubMed  CAS  Google Scholar 

  • Vijayaraghanavan R, Schaper M, Thompson R, Stock MF, Alarie Y (1993) Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol 67:478–490

    Article  Google Scholar 

  • Wagner EM, Bleecker ER, Permutt S, et al (1998) Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med 157:447–452

    PubMed  CAS  Google Scholar 

  • Walker C, Bauer W, Braun RK, Menz G, Braun P, Schwarz F, Hansel TT, Villiger B (1994) Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 150:1038–1048

    PubMed  CAS  Google Scholar 

  • Walz TM, Nishikawa BK, Malm C, Wasteson A (1993) Production of transforming growth factor alpha by normal human blood eosinophils. Leukemia 7:1531–1537

    PubMed  CAS  Google Scholar 

  • Wang JM, Rambaldi A, Biondi A, Chen ZG, Sanderson CJ, Mantovani A (1989) Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol 19:701–705

    Article  PubMed  CAS  Google Scholar 

  • Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD (1998) Interleukin-13: central mediator of allergic asthma. Science 282:2258–2261

    Article  PubMed  CAS  Google Scholar 

  • Yanai M, Sekizawa K, Ohrui T, et al (1992) Site of airway obstruction in pulmonary disease; direct measurement of intrabronchial pressure. J Appl Physiol 72:1016–1023

    PubMed  CAS  Google Scholar 

  • Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB (1995) Phenotype of cells expressing mRNA for Th2-type (interleukin 4 and interleukin 5) and Thl-type (interleukin 2 and interferon gamma) cytokines in broncho-alveolar lavage and bronchial biopsies from atopic asthmatics and normal control subjects. Am J Respir Cell Mol Biol 12:477–487

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Wegmann, M., Renz, H. (2005). Animal Models of Experimental Asthma. In: Zollner, T., Renz, H., Asadullah, K. (eds) Animal Models of T Cell-Mediated Skin Diseases. Ernst Schering Research Foundation Workshop, vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26811-1_4

Download citation

  • DOI: https://doi.org/10.1007/3-540-26811-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-21067-2

  • Online ISBN: 978-3-540-26811-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics