J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/06/2143/14 $2.00
Volume 185, Number 12, June 16, 1997 2143-2156

Interleukin-5 Expression in the Lung Epithelium of Transgenic Mice Leads to Pulmonary Changes Pathognomonic of Asthma

By James J. Lee,^* Michael P. McGarry, Steven C. Farmer,^* Karen L. Denzler,^* Kirsten A. Larson,^* Patricia E. Carrigan,^§ Ina E. Brenneise,^* Margaret A. Horton,^* Angela Haczku, Erwin W. Gelfand, George D. Leikauf,^§ and Nancy A. Lee^*

From the ^* Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona 85259;  Department of Laboratory Animal Resources, Roswell Park Cancer Institute, Buffalo, New York 14263; ^§ Department of Environmental Health, Molecular and Cellular Physiology and Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and  Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206

We have generated transgenic mice that constitutively express murine interleukin (IL)-5 in the lung epithelium. Airway expression of this cytokine resulted in a dramatic accumulation of peribronchial eosinophils and striking pathologic changes including the expansion of bronchusassociated lymphoid tissue (BALT), goblet cell hyperplasia, epithelial hypertrophy, and focal collagen deposition. These changes were also accompanied by eosinophil infiltration of the airway lumen. In addition, transgenic animals displayed airway hyperresponsiveness to methacholine in the absence of aerosolized antigen challenge. These findings demonstrate that lung-specific IL-5 expression can induce pathologic changes characteristic of asthma and may provide useful models to evaluate the efficacy of potential respiratory disease therapies or pharmaceuticals.

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• Wang, Z., Zheng, T., Zhu, Z., Homer, R. J., Riese, R. J., Chapman, H. A. , Jr., Shapiro, S. D., Elias, J. A. (2000). Interferon {{gamma}} Induction of Pulmonary Emphysema in the Adult Murine Lung. J. Exp. Med. 192: 1587-1600 [Abstract] [Full Text]  
• Malaviya, R., Chen, C.-L., Navara, C., Malaviya, R., Liu, X.-P., Keenan, M., Waurzyniak, B., Uckun, F. M. (2000). Treatment of Allergic Asthma by Targeting Janus Kinase 3-Dependent Leukotriene Synthesis in Mast Cells with 4-(3',5'-Dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97). J. Pharmacol. Exp. Ther. 295: 912-926 [Abstract] [Full Text]  
• Denzler, K. L., Farmer, S. C., Crosby, J. R., Borchers, M., Cieslewicz, G., Larson, K. A., Cormier-Regard, S., Lee, N. A., Lee, J. J. (2000). Eosinophil Major Basic Protein-1 Does Not Contribute to Allergen-Induced Airway Pathologies in Mouse Models of Asthma. J. Immunol. 165: 5509-5517 [Abstract] [Full Text]  
• Van Wauwe, J., Aerts, F., Cools, M., Deroose, F., Freyne, E., Goossens, J., Hermans, B., Lacrampe, J., Van Genechten, H., Van Gerven, F., Van Nyen, G. (2000). Identification of R146225 as a Novel, Orally Active Inhibitor of Interleukin-5 Biosynthesis. J. Pharmacol. Exp. Ther. 295: 655-661 [Abstract] [Full Text]  
• Herbert, D.'B. R., Lee, J. J., Lee, N. A., Nolan, T. J., Schad, G. A., Abraham, D. (2000). Role of IL-5 in Innate and Adaptive Immunity to Larval Strongyloides stercoralis in Mice. J. Immunol. 165: 4544-4551 [Abstract] [Full Text]  
• Tomaki, M., Zhao, L.-L., Lundahl, J., Sjostrand, M., Jordana, M., Linden, A., O'Byrne, P., Lotvall, J. (2000). Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor {alpha}. J. Immunol. 165: 4040-4050 [Abstract] [Full Text]  
• COYLE, A. J., LLOYD, C. M., GUTIERREZ-RAMOS, J.-C. (2000). Biotherapeutic Targets for the Treatment of Allergic Airway Disease. Am. J. Respir. Crit. Care Med. 162: S179-184 [Abstract] [Full Text]  
• Ochi, H., De Jesus, N. H., Hsieh, F. H., Austen, K. F., Boyce, J. A. (2000). IL-4 and -5 prime human mast cells for different profiles of IgE-dependent cytokine production. Proc. Natl. Acad. Sci. USA 10.1073/pnas.180318697v1 [Abstract] [Full Text]  
• Blyth, D. I., Wharton, T. F., Pedrick, M. S., Savage, T. J., Sanjar, S. (2000). Airway Subepithelial Fibrosis in a Murine Model of Atopic Asthma . Suppression by Dexamethasone or Anti-Interleukin-5 Antibody. Am. J. Respir. Cell Mol. Bio. 23: 241-246 [Abstract] [Full Text]  
• CHO, H. Y., HOTCHKISS, J. A., BENNETT, C. B., HARKEMA, J. R. (2000). Neutrophil-Dependent and Neutrophil-Independent Alterations in the Nasal Epithelium of Ozone-Exposed Rats. Am. J. Respir. Crit. Care Med. 162: 629-636 [Abstract] [Full Text]  
• McGraw, D. W., Forbes, S. L., Mak, J. C. W., Witte, D. P., Carrigan, P. E., Leikauf, G. D., Liggett, S. B. (2000). Transgenic overexpression of beta 2-adrenergic receptors in airway epithelial cells decreases bronchoconstriction. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L379-L389 [Abstract] [Full Text]  
• Holt, P G, Sly, P D (2000). Paediatric origins of adult lung diseases bullet 2: Prevention of adult asthma by early intervention during childhood: potential value of new generation immunomodulatory drugs. Thorax 55: 700-703 [Full Text]  
• Blackburn, M. R., Volmer, J. B., Thrasher, J. L., Zhong, H., Crosby, J. R., Lee, J. J., Kellems, R. E. (2000). Metabolic Consequences of Adenosine Deaminase Deficiency in Mice Are Associated with Defects in Alveogenesis, Pulmonary Inflammation, and Airway Obstruction. J. Exp. Med. 192: 159-170 [Abstract] [Full Text]  
• Webb, D. C., McKenzie, A. N. J., Koskinen, A. M. L., Yang, M., Mattes, J., Foster, P. S. (2000). Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity. J. Immunol. 165: 108-113 [Abstract] [Full Text]  
• Wills-Karp, M. (2000). Trophic Slime, Allergic Slime. Am. J. Respir. Cell Mol. Bio. 22: 637-639 [Full Text]  
• Hadeiba, H., Corry, D. B., Locksley, R. M. (2000). Baseline Airway Hyperreactivity in A/J Mice Is not Mediated by Cells of the Adaptive Immune System. J. Immunol. 164: 4933-4940 [Abstract] [Full Text]  
• van Scott, M. R., Justice, J. P., Bradfield, J. F., Enright, E., Sigounas, A., Sur, S. (2000). IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L667-L674 [Abstract] [Full Text]  
• Kobayashi, T., Miura, T., Haba, T., Sato, M., Serizawa, I., Nagai, H., Ishizaka, K. (2000). An Essential Role of Mast Cells in the Development of Airway Hyperresponsiveness in a Murine Asthma Model. J. Immunol. 164: 3855-3861 [Abstract] [Full Text]  
• Zuhdi Alimam, M., Piazza, F. M., Selby, D. M., Letwin, N., Huang, L., Rose, M. C. (2000). Muc-5/5ac Mucin Messenger RNA and Protein Expression Is a Marker of Goblet Cell Metaplasia in Murine Airways. Am. J. Respir. Cell Mol. Bio. 22: 253-260 [Abstract] [Full Text]  
• HACZKU, A., TAKEDA, K., HAMELMANN, E., LOADER, J., JOETHAM, A., REDAI, I., IRVIN, C. G., LEE, J. J., KIKUTANI, H., CONRAD, D., GELFAND, E. W. (2000). CD23 Exhibits Negative Regulatory Effects on Allergic Sensitization and Airway Hyperresponsiveness. Am. J. Respir. Crit. Care Med. 161: 952-960 [Abstract] [Full Text]  

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