Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma

Sergei I. Ochkur, Elizabeth Jacobsen, Cheryl A. Protheroe, Travis L. Biechele, Ralph S. Pero, Michael P. McGarry, Huiying Wang, Katie R. O'Neill, Dana C. Colbert, Thomas V. Colby, Huahao Shen, Michael R. Blackburn, Charles C. Irvin, James J. Lee, Nancy A Lee

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Mouse models of allergen provocation and/or transgenic gene expression have provided significant insights regarding the cellular, molecular, and immune responses linked to the pathologies occurring as a result of allergic respiratory inflammation. Nonetheless, the inability to replicate the eosinophil activities occurring in patients with asthma has limited their usefulness to understand the larger role(s) of eosinophils in disease pathologies. These limitations have led us to develop an allergen-naive double transgenic mouse model that expresses IL-5 systemically from mature T cells and eotaxin-2 locally from lung epithelial cells. We show that these mice develop several pulmonary pathologies representative of severe asthma, including structural remodeling events such as epithelial desquamation and mucus hypersecretion leading to airway obstruction, subepithelial fibrosis, airway smooth muscle hyperplasia, and pathophysiological changes exemplified by exacerbated methacholine-induced airway hyperresponsiveness. More importantly, and similar to human patients, the pulmonary pathologies observed are accompanied by extensive eosinophil degranulation. Genetic ablation of all eosinophils from this double transgenic model abolished the induced pulmonary pathologies, demonstrating that these pathologies are a consequence of one or more eosinophil effector functions.

Original languageEnglish (US)
Pages (from-to)7879-7889
Number of pages11
JournalJournal of Immunology
Volume178
Issue number12
StatePublished - Jun 15 2007

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Chemokine CCL24
Interleukin-5
Eosinophils
Asthma
Pathology
Inflammation
Lung
Allergens
Methacholine Chloride
Airway Obstruction
Mucus
Cellular Immunity
Transgenic Mice
Hyperplasia
Smooth Muscle
Fibrosis
Epithelial Cells
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma. / Ochkur, Sergei I.; Jacobsen, Elizabeth; Protheroe, Cheryl A.; Biechele, Travis L.; Pero, Ralph S.; McGarry, Michael P.; Wang, Huiying; O'Neill, Katie R.; Colbert, Dana C.; Colby, Thomas V.; Shen, Huahao; Blackburn, Michael R.; Irvin, Charles C.; Lee, James J.; Lee, Nancy A.

In: Journal of Immunology, Vol. 178, No. 12, 15.06.2007, p. 7879-7889.

Research output: Contribution to journalArticle

Ochkur, SI, Jacobsen, E, Protheroe, CA, Biechele, TL, Pero, RS, McGarry, MP, Wang, H, O'Neill, KR, Colbert, DC, Colby, TV, Shen, H, Blackburn, MR, Irvin, CC, Lee, JJ & Lee, NA 2007, 'Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma', Journal of Immunology, vol. 178, no. 12, pp. 7879-7889.
Ochkur, Sergei I. ; Jacobsen, Elizabeth ; Protheroe, Cheryl A. ; Biechele, Travis L. ; Pero, Ralph S. ; McGarry, Michael P. ; Wang, Huiying ; O'Neill, Katie R. ; Colbert, Dana C. ; Colby, Thomas V. ; Shen, Huahao ; Blackburn, Michael R. ; Irvin, Charles C. ; Lee, James J. ; Lee, Nancy A. / Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma. In: Journal of Immunology. 2007 ; Vol. 178, No. 12. pp. 7879-7889.
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