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

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

doi:10.1084/jem.185.12.2143

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Article| June 16 1997

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

James J. Lee,

James J. 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

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Michael P. McGarry,

Michael P. McGarry

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

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Steven C. Farmer,

Steven C. Farmer

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

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Karen L. Denzler,

Karen L. Denzler

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

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Kirsten A. Larson,

Kirsten A. Larson

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

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Patricia E. Carrigan,

Patricia E. Carrigan

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

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Ina E. Brenneise,

Ina E. Brenneise

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

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Margaret A. Horton,

Margaret A. Horton

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

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Angela Haczku,

Angela Haczku

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

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Erwin W. Gelfand,

Erwin W. Gelfand

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

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George D. Leikauf,

George D. Leikauf

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

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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

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Author and Article Information

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 , 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

Address correspondence to James J. Lee or Nancy A. Lee, Mayo Clinic Arizona, Samuel C. Johnson Medical Research Building, 13400 E. Shea Boulevard, Scottsdale, Arizona 85259.

These studies represent a considerable effort on the part of many individuals in addition to the cited authors. We wish to thank Drs. John McDonald and Jeffery Whitsett for their encouragement and assistance in bringing many of us together as part of a productive collaborative effort. We wish to thank the important technical assistance by Trella Mitchell and the help received by the Histology (Anita Jennings) and Transgenic Mouse (Suresh Savarirayan) core facilities. Insightful comments and interpretations of the lung histology were provided by Drs. Thomas Colby and Kevin Leslie. Critical reviews of the manuscript by Drs. John McDonald, Kevin Leslie, Gerald Gleich, and Eric Wieben were invaluable to the clarity of the work presented. We are indebted to the Mayo Clinic Arizona graphic artists Marvin Ruona and Julie Jensen for their dedicated work, Susan Bond and Merrilee Parker for their patience dealing with earlier versions of the manuscript, and our program assistant Beverly K. Pratley without whom we could not function as a productive laboratory.

Funds for these studies were provided by the Mayo Foundation and the Arizona Disease Control Research Commission.

¹Abbreviations used in this paper: AHR, airway hyperresponsiveness; BAL, bronchial alveolar lavage; BALT, bronchus-associated lymphoid tissue; H/E, hematoxylin/eosin; mMBP, anti-murine eosinophil granule major basic protein; Penh, enhanced pause; SPF, specific pathogen-free; WBC, white blood cell.

Received: January 23 1997

Revision Received: March 28 1997

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1997

J Exp Med (1997) 185 (12): 2143–2156.

https://doi.org/10.1084/jem.185.12.2143

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.

1997

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