Abstract
Allergic asthma is a worldwide public health problem and a major socioeconomic burden disease. It is a chronic inflammatory disease marked by airway eosinophilia and goblet cell hyperplasia with mucus hypersecretion. Mouse models have proven as a valuable tool for studying human asthma. In the present report we describe a comparison of mouse asthma models. The experiments were designed as follows: Group I was injected with ovalbumin (OVA, i.p.) on day 1 and challenged with 1% OVA (aerosol exposure) on days 14~21. Group II was injected on day 1, 14 and aerosol-immunized on days 14~21. Group III was injected on day 1, 14 and immunized by 1% OVA aerosol on days 18~21. We assessed asthma induction by determining the total number of white blood cells (WBC) and eosinophils as well as by measuring cytokine levels in bronchoalveolar lavage fluid (BALF). In addition, we evaluated the histopathological changes of the lungs and determined the concentration of immunoglobulin E (IgE) in serum. Total WBC, eosinophils, Th2 cytokines (IL-4, IL-13) and IgE were significantly increased in group I relative to the other groups. Moreover, histopathological studies show that group I mice show an increase in the infiltration of inflammatory cell-in peribronchial and perivascular areas as well as an overall increase in the number of mucus-containing goblet cells relative to other groups. These data suggest that group I can be a useful model for the study of human asthma pathobiology and the evaluation of existing and novel therapeutic agents.
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Abraham, W.M. (1995). Animal models of late bronchial responses. Eur. Respir. Rev., 5, 211–217.
Armin, B., Thomas, T. and David, A.G. (2008). Editorial: Experimental models of asthma. J. Occu. Med. and Toxicol., 3, Suppl 1, S1.
Barnes, P.J., Chung, K.F. and Page, C.P. (1998). Inflammatory mediators of asthma: an update. Pharmacol. Rev., 50, 515–596.
Blanchard, C., Mishra, A., Saito-Akei, H., Monk, P., Anderson, I. and Rothenberg, M.E. (2005). Inhibition of human inter-leukin-13-induced respiratory and esophageal inflammation by anti-human interleukin-13 antibody (CAT-354). Clin. Exp. Allergy, 35, 1096–1103.
Bousquet, J., Chanez, P., Lacoste, J.Y., Barneron, G., Gga-vanian, N., Enander, I., Venge, P., Ahlstedt, S., Simony-Lafontaine, J. and Goard, P. (1990). Eosinophilic inflammation in asthma. N. Engl. J. Med., 323, 1033–1039.
Bousquet, J., Jeffery, P.K., Busse, W.W., Johnson, M. and Vignola, A.M. (2000). Asthma: from bronchoconstriction to airways inflammation and remodeling. Am. J. Respir. Cht. Care. Med., 161, 1720–1745.
Cho, J.Y., Miller, M., Baek, K.J., Han. J.W., Nayar, J., Lee, S.Y., McElwain, K., McElwain, S., Friedman, S. and Broide, D.H. (2004). Inhibition of airway remodeling in IL-5 deficient mice. J. Clin. Invest, 113, 551–560.
De Weck, A.L., Mayer, P., Stumper, B., Schiessel, B. and Pickat, L. (1997). Dog allergy, a model for allergy genetics. Int. Arch. Allergy Immunol., 113, 55–57.
El-Hashim, A.Z., Wyss, D. and Zuany-Amorim, C. (2002). Kinetics of airway hyperresponsiveness and airway eosinophilia in BALB/c mice and their modulation by different dexamethasone treatment regimens. Pulmonary Pharmacol. & Thera., 15, 467–475.
Eric, R., Secor, J., William, E., Carson, I.V., Anurag, S., Mellisa, P., Linda, A., Guernsey, C.M., Schramm and Roger S.T. (2008) Oral bromelain attenuates inflammation in an oval-bumin-induced murine model of asthma. eCAM., 5, 61–69.
Flood-Page, P., Menzies-Gow, A., Phipps, S., Ying, S., Wangoo, A., Ludwig, M.S., Barnes, N., Robinson, D. and Kay, A.B. (2003). Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J. Clin. Invest., 112, 1029–1036.
Fred Wonga, W.S., Hua, Z. and Wupeng, L. (2007). Cys-teinyl leukotriene receptor antagonist MK-571 alters bron-choalveolar lavage fluid proteome in a mouse asthma model. Euro. J. Phar, 575, 134–141.
Fulkerson, P., Fischetti, C., Hassman, L., Nikolaidis, N.M. and Rothenberg, M.E. (2006). Persistent effects induced by IL-13 in the lung. Am. J. Respir. Cell. Mol. Biol., 35, 337–346.
Hamid, Q., Tulic, M.K., Liu, M.C. and Moqbel, R. (2003). Inflammatory cells in asthma: mechanisms and implications for therapy. J. Allergy Clin. Immunol., 111, S5–S17.
Heo, Y. and Kim, K.H. (2002). Development of subacute animal model to predict occurance of systemic anaphylaxis following vaccination and evaluation of various immuno-toxicological parameters. J. Toxicol. Pub. Health, 18, 205–213.
Hessel, E.M., Van Oosterhout, A.J., Hofstra, C.L., De Bie, J.J., Garssen, J., Van Loveren, H., et al. (1995). Bronchoconstriction and airway hyperresponsiveness after ovalbumin inhalation in sensitized mice. Eur. J. Pharmacol., 293, 401–412.
Humbert, M., Durham, S.R., Kimmitt, P., Powell, N., Assoufi, B., Pfister, R., Menz, G., Kay, A.B. and Corrigan, C.J. (1997). Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J. Allergy Clin. Immunol., 99, 657–665.
Kim, H.A. and Heo, Y. (2001). Significance of a highly specific and sensitive enzyme linked immunosorent assay on evaluation of environmental toxicant-mediated allergic responses. J. Toxicol. Pub. Health, 17, 197–199.
Itoh, K., Takahashi, E., Mukaiyama, O., Sathoh, Y. and Yamaguchi, T. (1996). Relationship between airway eosi-nophilia and airway hyperresponsiveness in a late asthmatic model of guinea pigs. Int. Arch. Allergy Immunol., 109, 86–94.
Jiang, J.H., Li, G. Z., Chai, O.H. and Song, C.H. (2005). Increased intraepithelial mast cells in pulmonary airways of mouse asthma model. The Korean J. Anat, 38, 173–179.
Johnson, P.R.A., Roth, M., Tamm, M., Hughes, M., Ge, Q., King, G., Burgess, J.K. and Black, J.L. (2001). Airway smooth muscle cell proliferation is increased in asthma. Am. J. Respir. Crit. Care Med., 164, 474–477.
Karol, M.H. (1994). Animal models of occupational asthma. Eur. Respir. J., 7, 555–568.
Kasaian, M.T., Donaldson, D.D., Tchistiakova, L., Marquette, K., Tan, X.Y., Ahmed, A., Jacobson, B.A., Widom, A., Cook, T.A., Xu, X., Barry, A.B., Goldman, S.J. and Abraham, W.M. (2007). Efficacy of IL-13 neutralization in a sheep model of experimental asthma. Am. J. Respir. Cell. Mol. Biol. 36, 368–376.
Kay, A.B., Barata, L., Meng, Q., Durham, S.R. and Ying, S. (1997). Eosinophils and eosinophil-associated cytokines in allergic inflammation. Int. Arch. Allergy Immunol, 113, 196–199.
Kazuhiko, S. and Masami, K. (2003). Mouse Model of Airway Remodeling. Ame. J. Res. Critical Care Med., 168, 959–967.
Kips, J.C. (2001). Cytokines in asthma. Eur. Respir. J. Suppl., 34, 24–33.
Kumar, R.K. and Foster, P.S. (2002). Modeling allergic asthma in mice: pitfalls and opportunities. Am. J. Respir. Cell. Mol. Biol., 27, 267–272.
Martin, L.B., Kita, H., Leiferman, K.M. and Gleich, G.J. (1996). Eosinophils in allergy: role in disease, degranulation and cytokines. Int. Arch. Allergy Immunol, 109, 207–215.
McDonald, D.M. (2001). Angiogenesis and remodeling of airway vasculature in chronic inflammation. Am. J. Respir. Crit Care Med., 164, 39–45.
Meryl, H., Karol, J.M., Matheson, R.W., Lange, R.L. and Michael, I.L. (2001). Use of tumor necrosis factor receptor (TNFR)-knockout mice to probe the mechanism of chemically-induced asthma J. Toxicol. Pub. Health, 17, 305–307.
Owen, C.E. (2007). Immunoglobulin E: role in asthma and allergic disease: lessons from the clinic. Pharmacol. Ther, 113, 121–133.
Padrid, P. (1992). Chronic lower airway disease in the dog and cat. Probl. Vet. Med. 4, 320–344.
Paramesh, H. (2002). Epidemiology of asthma in India. Indian J. Pediatr, 69, 309–312.
Park, S.J., Shin, W.H., Seo, J.W. and Kim, E.J. (2007). Anthocyanins inhibit airway inflammation and hyperre-sponsiveness in a murine asthma model. Food and Chemical Toxicol, 45, 1459–1467.
Rakesh, K.K., Cristna, H. and Paul, S.F. (2008) The “Classical” ovalbumin challenge model of asthma in mice. Current Drug Targets, 9, 485–494.
Sofia, F.R., William, R.F., Kenneth, J.B. and Emma, J.K. (2008) Establishing the phenotype in novel acute and chronic murine models of allergic asthma. Internal. Immunopharmcol. 8, 756–763.
Swirski, F.K., Sajic, D., Robbins, C.S., Gajewska, B.U., Jordana, M. and Stampfli, M.R. (2002). Chronic exposure to innocuous antigen in sensitized mice leads to suppressed airway eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor. J. Immunol. 169, 3499–3506.
Tattersfield A.E., Knox, A.J., Britton, J.R. and Hall, I.P. (2002). Asthma. Lancet, 360, 1313–1322.
Temelkovski, J., Hogan, S.P., Shepherd, D.R., Foster, P.S. and Kumar, R.K. (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.
Torres, R., Picado, C. and Mora F. (2005). Use of the mouse to unravel allergic asthma: a review of the pathogenesis of allergic asthma in mouse models and its similarity to the condition in humans. Arch. Bronconeumol. 41, 141–152.
Toward, T.J., Smith, N. and Broadley, K.J. (2004). Effect of phosphodiesterase-5 inhibitor, sidenafil (Viagra), in animal models of airways disease. Am. J. Respir. Crit. Care Med., 169, 227–234.
Weiss, K.B. and Sullivan, S.D. (2001). The health economics of asthma and rhinitis. I. Assessing the economic impact. J. Allergy Clin. Immunol, 107, 3–8.
Yang, G., Li, L., Volk, A., Emmell, E., Petley, T., Giles-Komar, J., Rafferty, P., Lakshminarayanan, M., Griswold, D.E., Bugelski, P.J. and Das, A.M. (2005). Therapeutic dosing with anti-interleukin-13 monoclonal antibody inhibits asthma progression in mice. J. Pharmacol. Exp. Ther, 313, 8–15.
Yang, G., Volk, A., Petley, T., Emmell, E., Giles-Komar, J., Shang, X., Li, J., Das, A.M., Shealy, D., Griswold, D.E. et al. (2004). Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling. Cytokine, 28, 224–232.
Yoshida, M., Watson, R.M., Rerecich, T. and O’Byrne, P.M. (2005). Different profiles of T-cell IKN-gamma and IL-12 in allergen-induced early and dual responders with asthma. J. Allergy Clin. Immunol., 115, 1004–1009.
Yuk, J.E., Woo, J.S., Yun, C.Y., Lee, J.S., Kim, J.H., Song, G.Y., Uang, E.J., Hur, I.K. and Kim, I.S. (2007). Effects of lactose-ß-sitosterol and β-sitosterol on ovalbumin-induced lung inflammation in actively sensitized mice. Inter. Immuno., 7, 1517–1527.
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Yang, YS., Yang, MJ., Cho, KH. et al. Study of a BALB/c Mouse Model for Allergic Asthma. Toxicol Res. 24, 253–261 (2008). https://doi.org/10.5487/TR.2008.24.4.253
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DOI: https://doi.org/10.5487/TR.2008.24.4.253